therapy
ECMO
December 05, 2009, 19:41 Filed in: therapy
ECMO
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Extracorporeal Membrane Oxygenation (ECMO) is a form of partial cardiopulmonary bypass used for long-term support of respiratory and/or cardiac function. This technology arose from cardiopulmonary bypass used for cardiac surgery. Initial systems used bubble oxygenators which were poorly suited for prolonged use because of their tendency to hemolyze blood. Membrane oxygenators made long-term use of ECMO possible. The first report of successful ECMO support of an adult was published by Hill in 1972.
Rationale
ECMO is primarily indicated for patients with such severe ventilation and/or oxygenation problems that they are unlikely to survive conventional mechanical ventilation. Examples of such patients would include those with the adult respiratory distress syndrome (ARDS) without major non-pulmonary organ failure who are failing mechanical ventilation or who are suffering from major barotrauma that makes adequate ventilation impossible. ECMO is only useful in cases where the primary lung insult is reversible in the absence of the usual oxygen toxicity and barotrauma caused by usual mechanical support. Since most patients who die of ARDS die of multi-system organ failure or sepsis, it would follow that most ARDS patients are not good candidates for ECMO. Another criteria often cited for qualifying a patient for ECMO treatment is a pre-treatment predicted mortality threshold, typically above 80-90%. Such a threshold makes ECMO, a new and as yet non-mainstream therapy, an ethically appealing option for otherwise hopeless cases. Unfortunately, the use of such a criteria preselects patients that may already be too sick to benefit from ECMO. If the pre-treatment mortality predictions are over-estimated, as they frequently are, then ECMO, as a treatment, may get more credit than it deserves in saving these patients' lives.
Techniques
ECMO currently comes in two varieties: venoarterial (VA), and venovenous (VV). VA ECMO takes deoxygenated blood from a central vein or the right atrium, pumps it past the oxygenator, and then returns the oxygenated blood, under pressure, to the arterial side of the circulation (typically to the aorta). This form of ECMO partially supports the cardiac output as the flow through the ECMO circuit is in addition to the normal cardiac output. VV ECMO takes blood from a large vein and returns oxygenated blood back to a large vein. VV ECMO does not support the circulation. VA ECMO helps support the cardiac output and delivers higher levels of oxygenation support than does VV ECMO. VA ECMO carries a higher risk of systemic emboli than does VV. VV ECMO systems may actually recirculate previously oxygenated blood depending on the placement of the inflow and outflow catheters. Another variant of VV ECMO is extracorporeal CO2 removal (ECCO2R). With this mode of support, oxygenation is provided by slow ventilation of the native lungs while CO2 removal is accomplished by the ECMO circuit. In all forms of ECMO, CO2 removal is more efficient than O2 addition because of the solubility and diffusion properties of CO2 relative to O2. In fact, CO2 normally has to be added to ECMO circuits to offset this efficiency at CO2 removal. The flow through the ECMO circuit is typically on the order of 100 mL/kg/minute. This would be from 25-75% of the cardiac output. This high flow requires the placement of large catheters into the circulation. For adults, the intravascular catheters may be 20 Fr or larger while 14 Fr catheters might be used in infants. These are generally placed by cut-down. Current circuits require the use of systemic anticoagulation with heparin to keep the systems patent. This anticoagulation is, in large part, responsible for bleeding complications that can be seen with the use of ECMO. Bleeding may occur either at the site of catheter insertion or at remote sites such as intracranial or the gastrointestinal tract. Future catheters with inpregnated heparin may obviate the need for systemic anticoagulation and would be expected to reduce bleeding complications. Once blood leaves the patient, it comes in contact with a gas-permeable membrane that allows gas exchange to occur between the blood and the gasses (oxygen and carbon dioxide) that are run into the oxygenator. Carbon dioxide levels leaving the oxygenator can be adjusted about as low as the physician wants while oxygen levels typically reach the 400-500 mm Hg level. Note that CO2 content varies fairly directly with partial pressure while O2 content follows the shape of the oxyhemoglobin dissociation curve. Under normobaric conditions, this limits the amount of oxygen that can be loaded into blood. If you were to try to predict the final mixed arterial oxygen content or partial pressure during VA ECMO, you would need to know the pulmonary venous oxygen content, the ECMO effluent oxygen content, and the % of cardiac output flowing through the ECMO circuit:
CaO2 = (EO x EF + NO x NF) / (EF + NF)
Where EO: ECMO oxygen content
EF: ECMO flow
NO: non-ECMO oxygen content
NF: non-ECMO flow
Predicting final arterial content during VV ECMO is more complex and cannot be easily calculated. During VV ECMO, the lungs may actually excrete oxygen rather than remove it from the inspired gas. Once ECMO has been started, the ventilator is typically reduced to minimal settings to prevent atelectasis and barotrauma. The FIO2 is lowered as much as possible, perhaps to room air. The ECMO flow rate is adjusted to the minimum needed to provide for adequate gas exchange and/or circulation support in the case of VA ECMO. ECMO is typically used for 7-12 days and is weaned when there is evidence of pulmonary improvement as indicated by compliance or radiologic appearance. ECMO can also be stopped if there are major complications or if the patient's condition is determined to be hopeless.
Complications
ECMO complications are those associated with cannulation (pneumothorax, vascular disruptions, bleeding, infection, emboli), those associated with systemic anticoagulation (GI bleeding, intracranial bleeding etc), and exsanguination resulting from circuit disruptions. These potential complications require that a trained ECMO technician be present at the bedside 24 hours per day in addition to the patient's usual nursing presence. As many as 30% of ECMO treated infants reported to the Extracorporeal Life Support Organization (ELSO) registry suffer some degree of CNS injury.
Patient Selection
As mentioned previously, usual ECMO criteria include patients with a severe reversible process that would result in a very high predicted mortality with conventional ventilatory support. The best candidates are those without multi-system organ failure that are otherwise considered to be salvageable. It would be expected, that once ECMO becomes safer and more accepted by physicians, that these criteria would be revised to eliminate the requirement for a very high predicted pre-treatment mortality. There are several ways to evaluate patients to determine if they are 'sick enough' for ECMO. APACHE and other scoring systems could be used to predict mortality. More frequently, indexes to assess refractory hypoxemia are used. The a:A ratio or A-a gradient can be used, but the oxygenation index (OI) is currently in more common use: OI = (FIO2) (MAP) / PaO2 An OI greater than 0.40-0.55 is thought to predict an 80% predicted mortality. Unfortunately, mortality predictors have been notoriously pessimistic since they are derived by looking at retrospective data and tend to do a poor job of predicting prospective results.
Evaluation of Results
ECMO is a difficult therapy to study and compare to conventional means of support. Ideally, a therapy like ECMO should be studied with a prospective randomized clinical trial where patients that meet an inclusion criteria are randomized to receive either ECMO or conventional therapy. Unfortunately, in such a study, the typical end-point would be the death of the patient and this is an end-point that most investigators and institutional review boards are uncomfortable with. As a result, studies comparing ECMO to conventional therapy typically include an escape clause of sorts that allows patients who are determined to have failed conventional therapy can get a trial of 'rescue' ECMO. The other main problem with studies of ECMO for adult patients are that there are very few patients who are sick enough to need ECMO that have reversible disease that ECMO might allow time for reversal of the process. Less than 20% of ARDS deaths are caused by respiratory failure while higher numbers of pediatric and neonatal deaths are caused by primary respiratory failure which would explain why ECMO would be more successful in pediatrics than it has proven to be in adult medicine.
In 1979 an NIH sponsored study compared ECMO with conventional support of patients with acute respiratory failure. Survival with ECMO was 9.5% while survival with conventional therapy was 8.3%. In this study, however, many of the included patients had end stage irreversible lung disease. Until recently, the above study all but stopped the use of ECMO in adults.
Today, there are about 85 ECMO centers worldwide and about 4,000 neonates have been treated (as of September 1990). All of these patients had predicted pre-ECMO mortality estimates greater than 80% (remember the problems with predicted mortality figures) and 83% survived with ECMO treatment. Infants with meconium aspiration syndrome had a 93% survival rate while patients with congenital diaphragmatic hernia had the lowest survival rate at 62%. In August 1986, Luciano Gattinoni reported the results of a study of 43 patients with an expected mortality of greater than 90%. He used ECCO2R (VV ECMO with low frequency ventilation) and had 21 survivors (48.8%). Lung function improved during ECMO in 72.8% of cases. His study was not controlled and again has the problem of the questionable validity of the 90% predicted mortality figure.
Conclusions
From the neonatal experience, it would appear that the key to making successful use of ECMO in adults is proper patient selection. The following indications and criteria are probably appropriate:
1. Primary reversible respiratory failure
VV ECMO: The patients should be failing conventional ventilatory support in that they have poor oxygenation and/or ventilation in spite of high ventilator settings that carry a high risk of lung damage from barotrauma and/or oxygen toxicity. These patients are rare but they do exist. ARDS with severe barotrauma might be an example of this indication if there is no multi-system organ failure.
2. Reversible cardiogenic shock
VA ECMO: This is a potential indication but reversible cardiogenic shock is a rare condition hence the fall in popularity of intra-aortic balloon pumps perhaps with the exception of being a bridge to transplant.
3. No multi-system organ failure
Patients with MSOF have a very high mortality rate even when ventilation and oxygenation are more than adequate. ECMO would not be expected to do more than prolong death.
4. No contraindications for anticoagulation
This may be obviated when heparin inpregnated ECMO circuits are available.
References
Hill JD, O'Brien TG, Murray JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock lung syndrome): Use of the Bramson membrane lung. N Engl J Med 1972;286;629-634. [First report of prolonged ECMO]
O'Rourke PP. ECMO: Where Have We Been? Where Are We Going? Resp Care 1991;36:7,683-694. [Good review article]
Gattinoni L, Pesenti A, Mascheroni D, et al. Low-Frequency Positive-Pressure Ventilation With Extracorporeal CO2 Removal in Severe Acute Respiratory Failure. JAMA 1986;256:881-886. [non-randomized, non-controlled report of results]
Gattinoni L, Pesenti A, Marcolin R, Damia G. Extracorporeal Support in Acute Respiratory Failure, Intensive Care World 1988;5:2,42-45. [another report of the above results basically]
Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane oxygenation in severe respiratory failure: A randomized prospective study. JAMA 1979;242:2193-2196. [This is the NIH study mentioned in the text]
O'Rourke PP, Crone RK, Vacanti JP, et al. Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: A prospective randomized study. Pediatrics 1989;84:957-963. [This study is interesting as consent was obtained for ECMO only after randomization so parents of patients assigned to conventional therapy didn't know they were in a study]
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Extracorporeal Membrane Oxygenation (ECMO) is a form of partial cardiopulmonary bypass used for long-term support of respiratory and/or cardiac function. This technology arose from cardiopulmonary bypass used for cardiac surgery. Initial systems used bubble oxygenators which were poorly suited for prolonged use because of their tendency to hemolyze blood. Membrane oxygenators made long-term use of ECMO possible. The first report of successful ECMO support of an adult was published by Hill in 1972.
Rationale
ECMO is primarily indicated for patients with such severe ventilation and/or oxygenation problems that they are unlikely to survive conventional mechanical ventilation. Examples of such patients would include those with the adult respiratory distress syndrome (ARDS) without major non-pulmonary organ failure who are failing mechanical ventilation or who are suffering from major barotrauma that makes adequate ventilation impossible. ECMO is only useful in cases where the primary lung insult is reversible in the absence of the usual oxygen toxicity and barotrauma caused by usual mechanical support. Since most patients who die of ARDS die of multi-system organ failure or sepsis, it would follow that most ARDS patients are not good candidates for ECMO. Another criteria often cited for qualifying a patient for ECMO treatment is a pre-treatment predicted mortality threshold, typically above 80-90%. Such a threshold makes ECMO, a new and as yet non-mainstream therapy, an ethically appealing option for otherwise hopeless cases. Unfortunately, the use of such a criteria preselects patients that may already be too sick to benefit from ECMO. If the pre-treatment mortality predictions are over-estimated, as they frequently are, then ECMO, as a treatment, may get more credit than it deserves in saving these patients' lives.
Techniques
ECMO currently comes in two varieties: venoarterial (VA), and venovenous (VV). VA ECMO takes deoxygenated blood from a central vein or the right atrium, pumps it past the oxygenator, and then returns the oxygenated blood, under pressure, to the arterial side of the circulation (typically to the aorta). This form of ECMO partially supports the cardiac output as the flow through the ECMO circuit is in addition to the normal cardiac output. VV ECMO takes blood from a large vein and returns oxygenated blood back to a large vein. VV ECMO does not support the circulation. VA ECMO helps support the cardiac output and delivers higher levels of oxygenation support than does VV ECMO. VA ECMO carries a higher risk of systemic emboli than does VV. VV ECMO systems may actually recirculate previously oxygenated blood depending on the placement of the inflow and outflow catheters. Another variant of VV ECMO is extracorporeal CO2 removal (ECCO2R). With this mode of support, oxygenation is provided by slow ventilation of the native lungs while CO2 removal is accomplished by the ECMO circuit. In all forms of ECMO, CO2 removal is more efficient than O2 addition because of the solubility and diffusion properties of CO2 relative to O2. In fact, CO2 normally has to be added to ECMO circuits to offset this efficiency at CO2 removal. The flow through the ECMO circuit is typically on the order of 100 mL/kg/minute. This would be from 25-75% of the cardiac output. This high flow requires the placement of large catheters into the circulation. For adults, the intravascular catheters may be 20 Fr or larger while 14 Fr catheters might be used in infants. These are generally placed by cut-down. Current circuits require the use of systemic anticoagulation with heparin to keep the systems patent. This anticoagulation is, in large part, responsible for bleeding complications that can be seen with the use of ECMO. Bleeding may occur either at the site of catheter insertion or at remote sites such as intracranial or the gastrointestinal tract. Future catheters with inpregnated heparin may obviate the need for systemic anticoagulation and would be expected to reduce bleeding complications. Once blood leaves the patient, it comes in contact with a gas-permeable membrane that allows gas exchange to occur between the blood and the gasses (oxygen and carbon dioxide) that are run into the oxygenator. Carbon dioxide levels leaving the oxygenator can be adjusted about as low as the physician wants while oxygen levels typically reach the 400-500 mm Hg level. Note that CO2 content varies fairly directly with partial pressure while O2 content follows the shape of the oxyhemoglobin dissociation curve. Under normobaric conditions, this limits the amount of oxygen that can be loaded into blood. If you were to try to predict the final mixed arterial oxygen content or partial pressure during VA ECMO, you would need to know the pulmonary venous oxygen content, the ECMO effluent oxygen content, and the % of cardiac output flowing through the ECMO circuit:
CaO2 = (EO x EF + NO x NF) / (EF + NF)
Where EO: ECMO oxygen content
EF: ECMO flow
NO: non-ECMO oxygen content
NF: non-ECMO flow
Predicting final arterial content during VV ECMO is more complex and cannot be easily calculated. During VV ECMO, the lungs may actually excrete oxygen rather than remove it from the inspired gas. Once ECMO has been started, the ventilator is typically reduced to minimal settings to prevent atelectasis and barotrauma. The FIO2 is lowered as much as possible, perhaps to room air. The ECMO flow rate is adjusted to the minimum needed to provide for adequate gas exchange and/or circulation support in the case of VA ECMO. ECMO is typically used for 7-12 days and is weaned when there is evidence of pulmonary improvement as indicated by compliance or radiologic appearance. ECMO can also be stopped if there are major complications or if the patient's condition is determined to be hopeless.
Complications
ECMO complications are those associated with cannulation (pneumothorax, vascular disruptions, bleeding, infection, emboli), those associated with systemic anticoagulation (GI bleeding, intracranial bleeding etc), and exsanguination resulting from circuit disruptions. These potential complications require that a trained ECMO technician be present at the bedside 24 hours per day in addition to the patient's usual nursing presence. As many as 30% of ECMO treated infants reported to the Extracorporeal Life Support Organization (ELSO) registry suffer some degree of CNS injury.
Patient Selection
As mentioned previously, usual ECMO criteria include patients with a severe reversible process that would result in a very high predicted mortality with conventional ventilatory support. The best candidates are those without multi-system organ failure that are otherwise considered to be salvageable. It would be expected, that once ECMO becomes safer and more accepted by physicians, that these criteria would be revised to eliminate the requirement for a very high predicted pre-treatment mortality. There are several ways to evaluate patients to determine if they are 'sick enough' for ECMO. APACHE and other scoring systems could be used to predict mortality. More frequently, indexes to assess refractory hypoxemia are used. The a:A ratio or A-a gradient can be used, but the oxygenation index (OI) is currently in more common use: OI = (FIO2) (MAP) / PaO2 An OI greater than 0.40-0.55 is thought to predict an 80% predicted mortality. Unfortunately, mortality predictors have been notoriously pessimistic since they are derived by looking at retrospective data and tend to do a poor job of predicting prospective results.
Evaluation of Results
ECMO is a difficult therapy to study and compare to conventional means of support. Ideally, a therapy like ECMO should be studied with a prospective randomized clinical trial where patients that meet an inclusion criteria are randomized to receive either ECMO or conventional therapy. Unfortunately, in such a study, the typical end-point would be the death of the patient and this is an end-point that most investigators and institutional review boards are uncomfortable with. As a result, studies comparing ECMO to conventional therapy typically include an escape clause of sorts that allows patients who are determined to have failed conventional therapy can get a trial of 'rescue' ECMO. The other main problem with studies of ECMO for adult patients are that there are very few patients who are sick enough to need ECMO that have reversible disease that ECMO might allow time for reversal of the process. Less than 20% of ARDS deaths are caused by respiratory failure while higher numbers of pediatric and neonatal deaths are caused by primary respiratory failure which would explain why ECMO would be more successful in pediatrics than it has proven to be in adult medicine.
In 1979 an NIH sponsored study compared ECMO with conventional support of patients with acute respiratory failure. Survival with ECMO was 9.5% while survival with conventional therapy was 8.3%. In this study, however, many of the included patients had end stage irreversible lung disease. Until recently, the above study all but stopped the use of ECMO in adults.
Today, there are about 85 ECMO centers worldwide and about 4,000 neonates have been treated (as of September 1990). All of these patients had predicted pre-ECMO mortality estimates greater than 80% (remember the problems with predicted mortality figures) and 83% survived with ECMO treatment. Infants with meconium aspiration syndrome had a 93% survival rate while patients with congenital diaphragmatic hernia had the lowest survival rate at 62%. In August 1986, Luciano Gattinoni reported the results of a study of 43 patients with an expected mortality of greater than 90%. He used ECCO2R (VV ECMO with low frequency ventilation) and had 21 survivors (48.8%). Lung function improved during ECMO in 72.8% of cases. His study was not controlled and again has the problem of the questionable validity of the 90% predicted mortality figure.
Conclusions
From the neonatal experience, it would appear that the key to making successful use of ECMO in adults is proper patient selection. The following indications and criteria are probably appropriate:
1. Primary reversible respiratory failure
VV ECMO: The patients should be failing conventional ventilatory support in that they have poor oxygenation and/or ventilation in spite of high ventilator settings that carry a high risk of lung damage from barotrauma and/or oxygen toxicity. These patients are rare but they do exist. ARDS with severe barotrauma might be an example of this indication if there is no multi-system organ failure.
2. Reversible cardiogenic shock
VA ECMO: This is a potential indication but reversible cardiogenic shock is a rare condition hence the fall in popularity of intra-aortic balloon pumps perhaps with the exception of being a bridge to transplant.
3. No multi-system organ failure
Patients with MSOF have a very high mortality rate even when ventilation and oxygenation are more than adequate. ECMO would not be expected to do more than prolong death.
4. No contraindications for anticoagulation
This may be obviated when heparin inpregnated ECMO circuits are available.
References
Hill JD, O'Brien TG, Murray JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock lung syndrome): Use of the Bramson membrane lung. N Engl J Med 1972;286;629-634. [First report of prolonged ECMO]
O'Rourke PP. ECMO: Where Have We Been? Where Are We Going? Resp Care 1991;36:7,683-694. [Good review article]
Gattinoni L, Pesenti A, Mascheroni D, et al. Low-Frequency Positive-Pressure Ventilation With Extracorporeal CO2 Removal in Severe Acute Respiratory Failure. JAMA 1986;256:881-886. [non-randomized, non-controlled report of results]
Gattinoni L, Pesenti A, Marcolin R, Damia G. Extracorporeal Support in Acute Respiratory Failure, Intensive Care World 1988;5:2,42-45. [another report of the above results basically]
Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane oxygenation in severe respiratory failure: A randomized prospective study. JAMA 1979;242:2193-2196. [This is the NIH study mentioned in the text]
O'Rourke PP, Crone RK, Vacanti JP, et al. Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: A prospective randomized study. Pediatrics 1989;84:957-963. [This study is interesting as consent was obtained for ECMO only after randomization so parents of patients assigned to conventional therapy didn't know they were in a study]
CO Poisoning
December 05, 2009, 19:40 Filed in: toxic gasses
Carbon Monoxide Poisoning
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Carbon monoxide (CO) poisoning is primarily a diagnostic challenge. It is a diagnosis that is seldom made, primarily because it is seldom considered. The gas is insidious as inhaling as little as 0.1% CO can be fatal. The gas has no odor, color, taste, or irritating quality. CO poisoning accounts for about 3,500 deaths annually and is the mechanism of half of all suicides. The physician must be sensitized to the possibility of CO exposure in many patients if the diagnosis is to be made. It doesn't take a rocket scientist to consider CO exposure in fire victims but patients exposed via other mechanisms are easily missed.
Where does CO come from?
CO is a product of incomplete combustion (complete combustion producesCO2 and H2O.) This obviously includes exposures to fires by victims and fire fighters but also includes smokers (cigars produce more CO than cigarettes - up to 20% CO Hb possible). Exhaust fumes are a common source of CO exposure. A recent report detailed high levels of CO exposure in enclosed pickup truck beds from a backdraft of exhaust fumes into the back of the truck. This is particularly common in children. For this reason, passengers should not ride in the back of enclosed pickup trucks. A local case resulted when a local hospital's mammography truck parked too close to a building allowing the truck's exhaust to be entrained into the diagnostic area of the truck. A radiologic technician skipped lung, staying in the van because she didn't feel good. Her main symptoms were nausea and headache. She later collapsed and was taken to an ER where it took some time for the possibility of CO exposure to be considered. A few hours after removal from exposure she was found to have a CO Hb level exceeding 20%. Other less obvious sources of CO exposure are endogenous. Methylene Chloride, an ingredient of paint thinners, can be converted to CO by the liver during metabolism with a longer than normal half-life of excretion. Porphyrin breakdown accounts for a normal 1% CO Hb during normal turnover of hemoglobin.
Why is CO toxic?
Most of us were taught that CO is toxic because of its effect of displacing oxygen from hemoglobin thus causing hypoxia. This is probably not the primary mechanism of CO toxicity. In 1975, Goldbaum conducted a study where three groups of dogs were compared. One group was exposed to CO until their CO Hb saturation was 13% (leaving 87% available for oxygen). All dogs in this group died. A second group was made 68% anemic, reducing the oxygen carrying capacity to 32% of normal. All dogs in this group lived. A third group was transfused with CO exposed blood until their CO Hb saturation was 60% and all of these dogs survived. Another animal study by Geyer removed blood from rats and perfused them with an artificial solution capable of oxygen transport but that did not carry CO. Upon exposure to a 10% CO environment, the rats did well (remember that 0.1% CO would normally be fatal). This suggests that hemoglobin binding by CO is necessary but not sufficient to cause toxicity. Interference with oxygen transport by hemoglobin must play a minor role in CO's toxicity. One should not be surprised if measurement of COHb levels by co-oximetry is a poor method to quantify meaningful CO exposure as high levels may be survivable while low levels may result in serious injury. It is thought, that CO, in dissolved form, directly interferes with cellular metabolism by binding with cytochrome oxidase enzymes such as cytochrome a3, the terminal enzyme in the electron transport chain. CO has 200 to 250 times greater affinity for hemoglobin than oxygen but also shifts the oxyhemoglobin curve leftward which makes oxygen bind more tightly which makes it more difficult for oxygen to leave hemoglobin at the tissue level.
CO Exposure Physiology
CO levels (COHb%) have a time course of elimination from the body. The elimination half-life of CO while breathing room air is 320 minutes. This drops to 90 minutes while breathing 100% oxygen and to 23 minutes with 100% oxygen under 3 atmospheres pressure (hyperbaric chamber). A 1% CO atmosphere can allow lethal concentrations to develop within 10 minutes. Hemoglobin acts as a sink or vacuum that quickly removes any inhaled CO from the alveolar gas. Symptoms develop more quickly in children and the elderly. Sicker and/or more active patients also do worse. Exercise, stress, and anemia make individuals more susceptible. Higher atmospheric concentrations and longer durations of exposure are also factors to be considered. In CO exposure victims where the exposure is fire related, one must remember to consider the effects of other frequently fire-associated toxins such as cyanide. Because of their higher oxygen demands, the brain and heart are most sensitive to the hypoxic effects of CO exposure. CNS involvement accounts for many of the signs of CO exposure. COHb levels below 20% are usually associated with nausea, headache and mild dyspnea. From 20-40%, vomiting, poor judgement, and visual disturbances (including cortical blindness) develop. Above 40%, ataxia, confusion, syncope, coma, seizures and tachypnea are found. COHb levels are not, prognostic. Deaths have been reported with very low CO levels. About 12% of patients have delayed neurological deficits often following an initial asymptomatic period of several days. The onset of these delayed symptoms varies from 1 to 21 days with a mean of 6 days. These changes include memory impairment and personality changes as well as dementia, cerebellar ataxia and dystonias.
Clinical Diagnosis
As mentioned previously, a clinical suspicion is very important in diagnosing CO exposures. Symptoms are non-specific and include headache, dizziness, nausea and vomiting. CO exposures in the winter (when most accidental CO exposures occur) are frequently misdiagnosed as influenza, particularly when whole families are involved as they frequently are if there is a malfunctioning heater or fireplace.
Laboratory Diagnosis
The CO Hb level can be measured with co-oximetry. Remember that SaO2 levels from blood gas machines are normally calculated based on the pH and PO2 and will thus not reflect reduced levels in cases of CO poisoning. With routine blood gasses, PO2's and SaO2's will be normal (or very high if oxygen is being administered). If the exposure is significant, a metabolic acidosis will be present, reflecting tissue hypoxia. An anion gap will frequently be present and serum lactate levels may be elevated. CO Hb levels are frequently greater than 10% (up to 10% levels can be obtained from heavy smokers). CO Hb levels greater than 60% are almost always fatal but fatalities and severe brain damage can result from patients with normal CO levels. Remember that the damage may be done once levels have returned to normal from normal excretion. EKG's may show tachycardia and evidence of ischemia. Psychometric testing will frequently show mental deficits that resolve with treatment and may be the most sensitive method of detecting significant CO exposure and also provide for a means to evaluate the effects of therapy.
Therapy
Initially, all patients with suspected CO exposure should be treated with 100% oxygen delivered by a tight fitting mask (non-rebreather or demand valve device). Patients who are unconscious should be intubated. Associated conditions (burns, trauma, cyanide poisoning) should be treated. Hyperbaric oxygen therapy (HBO) is considered to be standard of care for patients with significant exposure defined as any patient who has been unconscious, neurological symptoms beyond simple headache, evidence of myocardial ischemia (symptoms or EKG), COHb levels greater than 25%, or unexpected abnormalities on psychometric testing. HBO therapy results in faster reductions in CO Hb levels (this is of uncertain importance), it increases tissue oxygen levels, and decreases cerebral edema. HBO therapy is normally given with 3 atmospheres of pressure using 100% oxygen for 90 minutes every 8 hours for 24 hours. HBO therapy almost totally eliminates the development of delayed neurologic sequelae. These effects are related to removal of CO from peripheral binding sites and not from reduction of CO Hb levels.
Follow-up
Part of treating CO poisoning is to prevent future exposures. It is not unheard of to treat a whole family for CO exposure from home and to have the family return to the same contaminated atmosphere because of a lack of understanding of the risks and need for corrective action. Follow-up must also be provided for to look for delayed results of CO exposure. Late treatment with HBO has been shown to reverse some symptoms in some cases.
References
Goldbaum LR, Ramirez RG, Absalon KB: What is the mechanism of carbon monoxide toxicity? Aviat Space Environ Med 1975; 46:1289-1291.
Myers RAM, Snyder SK, Emhoff TA: Subacute sequelae of carbon monoxide poisoning. AnnEmerg Med 1985; 14:1163-1167.
Norkool DM, Kirkpatrick JN: Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: A review of 115 cases. Ann Emerg Med 1985; 14:1168-1171.
Turnbull, Timothy: Emergency Department Screening for Unsuspected Carbon Monoxide Exposure. Ann Emerg Med 17:478-489.
Stewart, RD: The Effect of Carbon Monoxide on Humans, J Occ Med 1976; 18:5.
Myers RAM: Are Arterial Blood Gases of Value in Treatment Decisions for Carbon Monoxide Poisoning? Crit Care Med 1989;17:139-142.
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Carbon monoxide (CO) poisoning is primarily a diagnostic challenge. It is a diagnosis that is seldom made, primarily because it is seldom considered. The gas is insidious as inhaling as little as 0.1% CO can be fatal. The gas has no odor, color, taste, or irritating quality. CO poisoning accounts for about 3,500 deaths annually and is the mechanism of half of all suicides. The physician must be sensitized to the possibility of CO exposure in many patients if the diagnosis is to be made. It doesn't take a rocket scientist to consider CO exposure in fire victims but patients exposed via other mechanisms are easily missed.
Where does CO come from?
CO is a product of incomplete combustion (complete combustion producesCO2 and H2O.) This obviously includes exposures to fires by victims and fire fighters but also includes smokers (cigars produce more CO than cigarettes - up to 20% CO Hb possible). Exhaust fumes are a common source of CO exposure. A recent report detailed high levels of CO exposure in enclosed pickup truck beds from a backdraft of exhaust fumes into the back of the truck. This is particularly common in children. For this reason, passengers should not ride in the back of enclosed pickup trucks. A local case resulted when a local hospital's mammography truck parked too close to a building allowing the truck's exhaust to be entrained into the diagnostic area of the truck. A radiologic technician skipped lung, staying in the van because she didn't feel good. Her main symptoms were nausea and headache. She later collapsed and was taken to an ER where it took some time for the possibility of CO exposure to be considered. A few hours after removal from exposure she was found to have a CO Hb level exceeding 20%. Other less obvious sources of CO exposure are endogenous. Methylene Chloride, an ingredient of paint thinners, can be converted to CO by the liver during metabolism with a longer than normal half-life of excretion. Porphyrin breakdown accounts for a normal 1% CO Hb during normal turnover of hemoglobin.
Why is CO toxic?
Most of us were taught that CO is toxic because of its effect of displacing oxygen from hemoglobin thus causing hypoxia. This is probably not the primary mechanism of CO toxicity. In 1975, Goldbaum conducted a study where three groups of dogs were compared. One group was exposed to CO until their CO Hb saturation was 13% (leaving 87% available for oxygen). All dogs in this group died. A second group was made 68% anemic, reducing the oxygen carrying capacity to 32% of normal. All dogs in this group lived. A third group was transfused with CO exposed blood until their CO Hb saturation was 60% and all of these dogs survived. Another animal study by Geyer removed blood from rats and perfused them with an artificial solution capable of oxygen transport but that did not carry CO. Upon exposure to a 10% CO environment, the rats did well (remember that 0.1% CO would normally be fatal). This suggests that hemoglobin binding by CO is necessary but not sufficient to cause toxicity. Interference with oxygen transport by hemoglobin must play a minor role in CO's toxicity. One should not be surprised if measurement of COHb levels by co-oximetry is a poor method to quantify meaningful CO exposure as high levels may be survivable while low levels may result in serious injury. It is thought, that CO, in dissolved form, directly interferes with cellular metabolism by binding with cytochrome oxidase enzymes such as cytochrome a3, the terminal enzyme in the electron transport chain. CO has 200 to 250 times greater affinity for hemoglobin than oxygen but also shifts the oxyhemoglobin curve leftward which makes oxygen bind more tightly which makes it more difficult for oxygen to leave hemoglobin at the tissue level.
CO Exposure Physiology
CO levels (COHb%) have a time course of elimination from the body. The elimination half-life of CO while breathing room air is 320 minutes. This drops to 90 minutes while breathing 100% oxygen and to 23 minutes with 100% oxygen under 3 atmospheres pressure (hyperbaric chamber). A 1% CO atmosphere can allow lethal concentrations to develop within 10 minutes. Hemoglobin acts as a sink or vacuum that quickly removes any inhaled CO from the alveolar gas. Symptoms develop more quickly in children and the elderly. Sicker and/or more active patients also do worse. Exercise, stress, and anemia make individuals more susceptible. Higher atmospheric concentrations and longer durations of exposure are also factors to be considered. In CO exposure victims where the exposure is fire related, one must remember to consider the effects of other frequently fire-associated toxins such as cyanide. Because of their higher oxygen demands, the brain and heart are most sensitive to the hypoxic effects of CO exposure. CNS involvement accounts for many of the signs of CO exposure. COHb levels below 20% are usually associated with nausea, headache and mild dyspnea. From 20-40%, vomiting, poor judgement, and visual disturbances (including cortical blindness) develop. Above 40%, ataxia, confusion, syncope, coma, seizures and tachypnea are found. COHb levels are not, prognostic. Deaths have been reported with very low CO levels. About 12% of patients have delayed neurological deficits often following an initial asymptomatic period of several days. The onset of these delayed symptoms varies from 1 to 21 days with a mean of 6 days. These changes include memory impairment and personality changes as well as dementia, cerebellar ataxia and dystonias.
Clinical Diagnosis
As mentioned previously, a clinical suspicion is very important in diagnosing CO exposures. Symptoms are non-specific and include headache, dizziness, nausea and vomiting. CO exposures in the winter (when most accidental CO exposures occur) are frequently misdiagnosed as influenza, particularly when whole families are involved as they frequently are if there is a malfunctioning heater or fireplace.
Laboratory Diagnosis
The CO Hb level can be measured with co-oximetry. Remember that SaO2 levels from blood gas machines are normally calculated based on the pH and PO2 and will thus not reflect reduced levels in cases of CO poisoning. With routine blood gasses, PO2's and SaO2's will be normal (or very high if oxygen is being administered). If the exposure is significant, a metabolic acidosis will be present, reflecting tissue hypoxia. An anion gap will frequently be present and serum lactate levels may be elevated. CO Hb levels are frequently greater than 10% (up to 10% levels can be obtained from heavy smokers). CO Hb levels greater than 60% are almost always fatal but fatalities and severe brain damage can result from patients with normal CO levels. Remember that the damage may be done once levels have returned to normal from normal excretion. EKG's may show tachycardia and evidence of ischemia. Psychometric testing will frequently show mental deficits that resolve with treatment and may be the most sensitive method of detecting significant CO exposure and also provide for a means to evaluate the effects of therapy.
Therapy
Initially, all patients with suspected CO exposure should be treated with 100% oxygen delivered by a tight fitting mask (non-rebreather or demand valve device). Patients who are unconscious should be intubated. Associated conditions (burns, trauma, cyanide poisoning) should be treated. Hyperbaric oxygen therapy (HBO) is considered to be standard of care for patients with significant exposure defined as any patient who has been unconscious, neurological symptoms beyond simple headache, evidence of myocardial ischemia (symptoms or EKG), COHb levels greater than 25%, or unexpected abnormalities on psychometric testing. HBO therapy results in faster reductions in CO Hb levels (this is of uncertain importance), it increases tissue oxygen levels, and decreases cerebral edema. HBO therapy is normally given with 3 atmospheres of pressure using 100% oxygen for 90 minutes every 8 hours for 24 hours. HBO therapy almost totally eliminates the development of delayed neurologic sequelae. These effects are related to removal of CO from peripheral binding sites and not from reduction of CO Hb levels.
Follow-up
Part of treating CO poisoning is to prevent future exposures. It is not unheard of to treat a whole family for CO exposure from home and to have the family return to the same contaminated atmosphere because of a lack of understanding of the risks and need for corrective action. Follow-up must also be provided for to look for delayed results of CO exposure. Late treatment with HBO has been shown to reverse some symptoms in some cases.
References
Goldbaum LR, Ramirez RG, Absalon KB: What is the mechanism of carbon monoxide toxicity? Aviat Space Environ Med 1975; 46:1289-1291.
Myers RAM, Snyder SK, Emhoff TA: Subacute sequelae of carbon monoxide poisoning. AnnEmerg Med 1985; 14:1163-1167.
Norkool DM, Kirkpatrick JN: Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: A review of 115 cases. Ann Emerg Med 1985; 14:1168-1171.
Turnbull, Timothy: Emergency Department Screening for Unsuspected Carbon Monoxide Exposure. Ann Emerg Med 17:478-489.
Stewart, RD: The Effect of Carbon Monoxide on Humans, J Occ Med 1976; 18:5.
Myers RAM: Are Arterial Blood Gases of Value in Treatment Decisions for Carbon Monoxide Poisoning? Crit Care Med 1989;17:139-142.
Severe Asthma
December 05, 2009, 19:40 Filed in: asthma
Life Threatening Asthma
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Asthma mortality has been increasing in recent years. Various experts have debated why this is so but several facts are apparent from the available data. First, most patients who die of asthma do not die in the hospital. Most do not die suddenly and have frequently been in the midst of an exacerbation for several days. Near fatal asthma is a risk factor for fatal asthma. Many, if not most, in-hospital asthma fatalities are a result of barotrauma. Clearly, outpatient asthma mortality could be improved by identifying those patient s at risk for fatal asthma and making sure they know when to seek medical care. Inpatient asthma mortality requires recognition, on the part of the care giver, of the causes and prevention of barotrauma.
Pathophysiology
Asthma has been called eosinophillic bronchitis which reflects the important role of eosinophils in mediating the asthmatic response. Everyone has some degree of airway reactivity which means that an inflammatory response will be elicited in anyone if the stimulus is strong enough. For some people it might take Clorox fumes, histamine, or methacholine to elicit this response while for others mere exposure to cold air could lead to the same result. Bronchial provocation testing is a pulmonary function test where a known airway irritant such as methacholine or histamine is aerosolized with pre and post exposure FEV1 measurements to determine the threshold dose necessary to bring about a given decrease in FEV1. A patient with severe asthma would require a small dose of the irritant while a patient with very non-reactive airways would require a higher dose to get the same decrease in lung function. Airway reactivity may be an inherited trait or it may result from a chemical or biological exposure, lasting long after the exposure has come and gone. Once a sufficient stimulus has reached the patient, a cascade of events takes place involving many chemical mediators of inflammation. These mediators result in inflammation (infiltration of tissues by inflammatory cells), edema, mucus hypersecretion, and smooth muscle contraction (bronchospasm).
Natural History
Just as airway reactivity, varies from person to person, the typical history of an asthmatic varies. Some patients will only be symptomatic as children while others will only become symptomatic in middle age, perhaps as a component of other chronic lung diseases. One important characteristic of asthma is that lung function should be essentially normal between exacerbations, unlike the emphysema patient, who always has abnormal lung function. This is why bronchial provocation testing is sometimes required to actually diagnose asthma since routine pulmonary function studies may frequently be normal when a patient is doing well. In a particular asthmatic attack, there are really two phases consisting of the early (histamine related) and late (inflammatory) reactions. The early reaction typically lasts for the first hour of treatment and results in an early response to therapy that may then relapse into the later, second phase reaction two to eight hours later. Because of this biphasic nature of a typical asthma attack, one must be careful not to discharge a patient from the emergency department too soon only to have a severe relapse occur away from the hospital. The initial reaction tends to respond well to inhaled bronchodilator agents while the late response requires the use of corticosteroids that have a delayed action thus they should be given early during the patient's ER visit to avoid the second stage relapse.
Initial Evaluation
The initial evaluation of the asthmatic patient should be intended to determine which patients are at risk for dying from their asthma but to prevent inappropriate ER discharges and to help determine the course of therapy to be used. The initial evaluation of an asthma attack consists of the physical examination and peak expiratory flow measurement. Breath sounds are an important part of the physical examination but it is easy to misjudge the severity of an attack using breath sounds. Many patients with severely reduced lung function will have fairly silent chests with little audible wheezing. As they improve with therapy, their wheezing may become much louder as wheezing is dependent upon airflow. Other physical findings associated with severe asthma include cyanosis (a very grim finding), altered mentation (time to intubate), increased use of accessory muscles of respiration, increased pulsus parodoxis, upright posture, and absence of breath sounds. Peak flow measurement is fairly simple and inexpensive and can objectively (within the limits of patient effort) stage airway obstruction much more accurately than physical examination and should be a part of every asthmatic's initial ER evaluation. PEFR (Peak Expiratory Expiratory Flow Rate) measurement is used not only to stage the disease but also to assess the response, or lack of response, to therapy. All patients with more than mild asthma should have their own PEFR meters that they keep at home so they will know their own normals and can give physicians and others objective information on the severity of a given attack over the telephone. For most of my adult asthmatic patients that have normal PEFR readings in the 300-400 LPM range, I advise them to notify me if their PEFR falls below 250 LPM with treatment and to expect that I'll probably put them on a tapering dose of oral steroids and I tell them that if their PEFR falls below 150 LPM they need to get to the ER, via the 911 system if possible as patients tend to develop respiratory failure at PEFR values below about 80 LPM. PEFR meters cost less than $20 and last until you step on them. Patients with severe asthma should have chest radiographs, primarily to look for evidence of infection (pneumonia) and barotrauma (pneumothorax or pneumomediastinum). These are not that useful in milder cases and rarely show more than mild hyperinflation. Blood gasses don't add much to acute asthma management prior to intubation since intubation should be based primarily on ability to oxygenate and altered mental status rather than any particular value for pH or PCO2.
Initial Treatment
The initial priority in asthma therapy is providing oxygen (there have been many malpractice suits lost because this step was skipped). Next comes the use of inhaled beta-2 agonist medications. Studies have been done that basically show little advantage of using nebulizers as opposed to repeated use of metered dose inhalers though most physicians tend to use nebulizers since the acutely dyspneic patient will frequently not be likely to be an expert at MDI use. On any ER patient presenting with asthma, I go ahead and establish IV access and give an initial high dose of steroid, typically Solu-medrol. Again, oral steroids work almost as quickly as IV but I tend to at least give the first dose IV as many of these patients will be borderline theophylline toxic and will be at risk of vomiting which will raise the question of whether the oral medication was actually delivered adequately. Inhaled anticholinergic drugs such as Atrovent or Atropine can be given but I've not been impressed with their efficacy in my experience (though I'll try most anything in the non-responding patient with severe asthma). Theophylline and Aminophylline are falling out of favor in the acute management of asthma as many studies in recent years have failed to show any additional benefit in terms of improved lung function or prevented hospital admission when theophylline products are added to beta-2 agonist therapy. There is some thought that these products might have some usefulness in the late response or perhaps used as anti-inflammatory agents but bottom line data is lacking. Theophylline products have a much higher toxicity and many patients presenting to the ER will already have toxic levels. Given the relative lack of efficacy when compared to beta-2 agonist agents, one should be very careful if they are used, and loading doses should generally be avoided in patients in whom a drug level measurement is not available prior to the bolus.
How to dose aerosolized medications
Aerosol therapy is a very inexact science. There is very little relationship between the amount of medication put in a nebulizer cup and the amount actually delivered to the site of action in a given patient. The percentage of a nebulized dose of a drug that is actually delivered to the site of action is influenced by patient size (smaller patients have smaller minute volumes and thus breath in less drug), airway size (smaller airways result in more rain out before the site of action), breathing pattern (higher inspiratory flows result in more inertial impaction of droplets before the site of action), nebulizer used (this influences particle size and aerosol density), flow rate of the driving gas, mask or mouthpiece type in use, mouth vs nose breathing, use of airways such as endotracheal tubes, use of ventilators to deliver the medications, placement of nebulizers in ventilator circuits, whether the ventilator is a volume ventilator or a continuous flow system and probably many other factors. Because of these problems, many of which are not controllable, dosage should be based on patient response, good and bad (i.e. give enough to get the effect you're looking for and back off when toxic effects become unmanageable). In pediatric patients (or smaller patients in general) it will be necessary to actually increase the amount of drug placed in the nebulizer to get similar therapeutic effects as they have several factors (smaller minute volumes and smaller airways) that result in their automatically getting less drug to the site of action. In the severe asthmatic, I typically use a standard concentration of drug (i.e. 0.5 cc in 2.5 cc of saline in the case of albuterol) and either give this aerosol continuously or via rapidly repeated doses until the patient responds with improved flow rates or gets unacceptable side effects (which are rarely encountered). I have given albuterol by continuous nebulization as long as 48 hours around the clock in a few severe patients with little trouble though electrolytes such as potassium and magnesium need to be monitored during therapy as beta-2 agonists will lower these.
When & Whether to Intubate
Why ask why? Remember that one of the largest causes of mortality in acute asthma in hospitalized patients is a result of barotrauma. Because of the very prolonged time constants in asthmatics (high airway resistance causing longer passive expiratory times), any mechanical ventilation using a respiratory rate much higher than 4 or so breaths per minute will result in a dangerous sequence of events. First, there will be air-trapping owing to inadequate expiratory time, this then leads to increased alveolar pressure and Auto-PEEP, which, in turn, leads to reduced venous return, a cardiac tamponade effect, and reduced cardiac output and blood pressure. It is not unusual for Auto-PEEP levels to exceed 30 cm H2O pressure in asthmatics, even those ventilated at respiratory rates less than 10 breaths per minute. Remember that in most asthmatics in respiratory failure, the problem is not one of muscle strength or even oxygenation but is one of respiratory mechanics, namely airway resistance, that is incompatible with effective ventilation at normal minute volumes. Because of these factors, it can be dangerous to put a patient with an acute severe asthma attack on a mechanical ventilator. The other side of this issue, of course, is that patients can die of respiratory failure and/or hypoxia thus one needs to know when the risks of respiratory failure exceed the risks of the treatment (ventilation). There are no absolute rules here but think about how respiratory failure results in death. The primary mechanism is hypoxia. Few patients die because their PaCO2 gets too high or because their pH gets too low. Hence, if adequate oxygenation can be maintained, there is still some time to direct therapy toward the underlying cause of respiratory failure, namely, the increased airway resistance. Again, all acute asthmatics should receive oxygen therapy. This buys time for other more definitive therapy to work. Watch for evidence of muscle fatigue and/or CO2 narcosis (which will eventually result in respiratory arrest). Typical signs are decreased respiratory effort in spite of increased loads, and altered mental status. My general method is to hold off on intubating an asthmatic until I'm unable to maintain adequate oxygenation or until the patient develops altered mental status (confusion, unresponsiveness, coma etc). Until these indicators are present, there is still time (though maybe not much time) to continue continuous inhaled beta-2 agonist therapy and steroids. Using this method I've had patients with CO2's transiently in the 90's stay awake and alert and wind up not needing the ventilator after another 15 minutes of aerosol therapy. This sort of approach, of course, requires constant monitoring by the physician at the bedside with frequent (if not continuous) assessment and re-assessment of the response to therapy.
After Intubation
Remember that as outlined above, intubation and mechanical ventilation are not a treatment for asthma but are only a treatment for respiratory failure and/or hypoxia. Once a patient is intubated, the treatment for asthma should be continued if not intensified with the use of continuous aerosolized bronchodilators and steroids, as well as IV steroids and optionally IV bronchodilators (usually Brethine (terbutaline)). The goals of mechanical ventilation in acute asthma are primarily to keep a patient alive while you wait on the asthma therapy to work, hopefully without killing the patient with the ventilator. Normal blood gasses are NOT the goal of mechanical ventilation in asthma. Adequate oxygenation with a minimum of barotrauma is the goal. It is frequently necessary to use very low respiratory rates (less than 6 breaths per minute in some cases) to avoid dangerous Auto-PEEP and its resultant sequelae. Patients, should in most cases, be pharmacologically sedated and paralyzed both to prevent dyssynchronous ventilation (bucking the vent) and to decrease the rate of metabolism and thus the requirement for ventilation and oxygenation. Fever should be treated to lower the metabolic rate if it is present. Auto-PEEP should be measured hourly initially and adjusted to a safe level (probably less than 10 in most patients though IV volume loading of the patient will make them more tolerant from a blood pressure stand-point). As Auto-PEEP decreases (signifying a reduced airway resistance) the respiratory rate can slowly be increased to correct the expected respiratory acidosis that most severe asthmatics on the ventilator will have when ventilated at low rates. Once breath sounds are clearing up, the continuous bronchodilator dosing can be made intermittent and sedation and paralysis can be weaned as can the ventilator itself in most cases. In most cases, mechanical ventilation will only be necessary for a few days (sometimes just a few hours will be adequate) though I've had some difficult cases require ventilation as long as two weeks with severe wheezing until right before weaning.
After Extubation
Patients who have been mechanically ventilated for asthma are in a very high risk group for mortality from asthma. They and their families should know this so they will take future attacks very seriously. They should be reminded that most asthma mortality occurs outside of the hospital and they should be very familiar with using a peak flow meter to monitor their progress.
References
Olsen GN: Asthma Concepts & Control in Olsen, GN: Basic Handouts in Pulmonary Medicine, 2/92.
Nowak RM, Pensler MI, Sarkar DD, et al. Comparison of peak expiratory flow and FEV1.0 admission criteria for acute bronchial asthma. Ann Emer Med 1982; 11:64-69.
Guidelines for the Diagnosis and Mangement of Asthma, National Heart, Lung, and Blood Institute, NIH, US Dept HHS, August 1991.
Miller TP: Identification, treatment of adults at increased risk of fatal asthma, Today in Medicine, Nov/Dec 1992.
Fish, JE: Status Asthmaticus in Current Therapy in Allergy, Immunology and Rheumatology.
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Asthma mortality has been increasing in recent years. Various experts have debated why this is so but several facts are apparent from the available data. First, most patients who die of asthma do not die in the hospital. Most do not die suddenly and have frequently been in the midst of an exacerbation for several days. Near fatal asthma is a risk factor for fatal asthma. Many, if not most, in-hospital asthma fatalities are a result of barotrauma. Clearly, outpatient asthma mortality could be improved by identifying those patient s at risk for fatal asthma and making sure they know when to seek medical care. Inpatient asthma mortality requires recognition, on the part of the care giver, of the causes and prevention of barotrauma.
Pathophysiology
Asthma has been called eosinophillic bronchitis which reflects the important role of eosinophils in mediating the asthmatic response. Everyone has some degree of airway reactivity which means that an inflammatory response will be elicited in anyone if the stimulus is strong enough. For some people it might take Clorox fumes, histamine, or methacholine to elicit this response while for others mere exposure to cold air could lead to the same result. Bronchial provocation testing is a pulmonary function test where a known airway irritant such as methacholine or histamine is aerosolized with pre and post exposure FEV1 measurements to determine the threshold dose necessary to bring about a given decrease in FEV1. A patient with severe asthma would require a small dose of the irritant while a patient with very non-reactive airways would require a higher dose to get the same decrease in lung function. Airway reactivity may be an inherited trait or it may result from a chemical or biological exposure, lasting long after the exposure has come and gone. Once a sufficient stimulus has reached the patient, a cascade of events takes place involving many chemical mediators of inflammation. These mediators result in inflammation (infiltration of tissues by inflammatory cells), edema, mucus hypersecretion, and smooth muscle contraction (bronchospasm).
Natural History
Just as airway reactivity, varies from person to person, the typical history of an asthmatic varies. Some patients will only be symptomatic as children while others will only become symptomatic in middle age, perhaps as a component of other chronic lung diseases. One important characteristic of asthma is that lung function should be essentially normal between exacerbations, unlike the emphysema patient, who always has abnormal lung function. This is why bronchial provocation testing is sometimes required to actually diagnose asthma since routine pulmonary function studies may frequently be normal when a patient is doing well. In a particular asthmatic attack, there are really two phases consisting of the early (histamine related) and late (inflammatory) reactions. The early reaction typically lasts for the first hour of treatment and results in an early response to therapy that may then relapse into the later, second phase reaction two to eight hours later. Because of this biphasic nature of a typical asthma attack, one must be careful not to discharge a patient from the emergency department too soon only to have a severe relapse occur away from the hospital. The initial reaction tends to respond well to inhaled bronchodilator agents while the late response requires the use of corticosteroids that have a delayed action thus they should be given early during the patient's ER visit to avoid the second stage relapse.
Initial Evaluation
The initial evaluation of the asthmatic patient should be intended to determine which patients are at risk for dying from their asthma but to prevent inappropriate ER discharges and to help determine the course of therapy to be used. The initial evaluation of an asthma attack consists of the physical examination and peak expiratory flow measurement. Breath sounds are an important part of the physical examination but it is easy to misjudge the severity of an attack using breath sounds. Many patients with severely reduced lung function will have fairly silent chests with little audible wheezing. As they improve with therapy, their wheezing may become much louder as wheezing is dependent upon airflow. Other physical findings associated with severe asthma include cyanosis (a very grim finding), altered mentation (time to intubate), increased use of accessory muscles of respiration, increased pulsus parodoxis, upright posture, and absence of breath sounds. Peak flow measurement is fairly simple and inexpensive and can objectively (within the limits of patient effort) stage airway obstruction much more accurately than physical examination and should be a part of every asthmatic's initial ER evaluation. PEFR (Peak Expiratory Expiratory Flow Rate) measurement is used not only to stage the disease but also to assess the response, or lack of response, to therapy. All patients with more than mild asthma should have their own PEFR meters that they keep at home so they will know their own normals and can give physicians and others objective information on the severity of a given attack over the telephone. For most of my adult asthmatic patients that have normal PEFR readings in the 300-400 LPM range, I advise them to notify me if their PEFR falls below 250 LPM with treatment and to expect that I'll probably put them on a tapering dose of oral steroids and I tell them that if their PEFR falls below 150 LPM they need to get to the ER, via the 911 system if possible as patients tend to develop respiratory failure at PEFR values below about 80 LPM. PEFR meters cost less than $20 and last until you step on them. Patients with severe asthma should have chest radiographs, primarily to look for evidence of infection (pneumonia) and barotrauma (pneumothorax or pneumomediastinum). These are not that useful in milder cases and rarely show more than mild hyperinflation. Blood gasses don't add much to acute asthma management prior to intubation since intubation should be based primarily on ability to oxygenate and altered mental status rather than any particular value for pH or PCO2.
Initial Treatment
The initial priority in asthma therapy is providing oxygen (there have been many malpractice suits lost because this step was skipped). Next comes the use of inhaled beta-2 agonist medications. Studies have been done that basically show little advantage of using nebulizers as opposed to repeated use of metered dose inhalers though most physicians tend to use nebulizers since the acutely dyspneic patient will frequently not be likely to be an expert at MDI use. On any ER patient presenting with asthma, I go ahead and establish IV access and give an initial high dose of steroid, typically Solu-medrol. Again, oral steroids work almost as quickly as IV but I tend to at least give the first dose IV as many of these patients will be borderline theophylline toxic and will be at risk of vomiting which will raise the question of whether the oral medication was actually delivered adequately. Inhaled anticholinergic drugs such as Atrovent or Atropine can be given but I've not been impressed with their efficacy in my experience (though I'll try most anything in the non-responding patient with severe asthma). Theophylline and Aminophylline are falling out of favor in the acute management of asthma as many studies in recent years have failed to show any additional benefit in terms of improved lung function or prevented hospital admission when theophylline products are added to beta-2 agonist therapy. There is some thought that these products might have some usefulness in the late response or perhaps used as anti-inflammatory agents but bottom line data is lacking. Theophylline products have a much higher toxicity and many patients presenting to the ER will already have toxic levels. Given the relative lack of efficacy when compared to beta-2 agonist agents, one should be very careful if they are used, and loading doses should generally be avoided in patients in whom a drug level measurement is not available prior to the bolus.
How to dose aerosolized medications
Aerosol therapy is a very inexact science. There is very little relationship between the amount of medication put in a nebulizer cup and the amount actually delivered to the site of action in a given patient. The percentage of a nebulized dose of a drug that is actually delivered to the site of action is influenced by patient size (smaller patients have smaller minute volumes and thus breath in less drug), airway size (smaller airways result in more rain out before the site of action), breathing pattern (higher inspiratory flows result in more inertial impaction of droplets before the site of action), nebulizer used (this influences particle size and aerosol density), flow rate of the driving gas, mask or mouthpiece type in use, mouth vs nose breathing, use of airways such as endotracheal tubes, use of ventilators to deliver the medications, placement of nebulizers in ventilator circuits, whether the ventilator is a volume ventilator or a continuous flow system and probably many other factors. Because of these problems, many of which are not controllable, dosage should be based on patient response, good and bad (i.e. give enough to get the effect you're looking for and back off when toxic effects become unmanageable). In pediatric patients (or smaller patients in general) it will be necessary to actually increase the amount of drug placed in the nebulizer to get similar therapeutic effects as they have several factors (smaller minute volumes and smaller airways) that result in their automatically getting less drug to the site of action. In the severe asthmatic, I typically use a standard concentration of drug (i.e. 0.5 cc in 2.5 cc of saline in the case of albuterol) and either give this aerosol continuously or via rapidly repeated doses until the patient responds with improved flow rates or gets unacceptable side effects (which are rarely encountered). I have given albuterol by continuous nebulization as long as 48 hours around the clock in a few severe patients with little trouble though electrolytes such as potassium and magnesium need to be monitored during therapy as beta-2 agonists will lower these.
When & Whether to Intubate
Why ask why? Remember that one of the largest causes of mortality in acute asthma in hospitalized patients is a result of barotrauma. Because of the very prolonged time constants in asthmatics (high airway resistance causing longer passive expiratory times), any mechanical ventilation using a respiratory rate much higher than 4 or so breaths per minute will result in a dangerous sequence of events. First, there will be air-trapping owing to inadequate expiratory time, this then leads to increased alveolar pressure and Auto-PEEP, which, in turn, leads to reduced venous return, a cardiac tamponade effect, and reduced cardiac output and blood pressure. It is not unusual for Auto-PEEP levels to exceed 30 cm H2O pressure in asthmatics, even those ventilated at respiratory rates less than 10 breaths per minute. Remember that in most asthmatics in respiratory failure, the problem is not one of muscle strength or even oxygenation but is one of respiratory mechanics, namely airway resistance, that is incompatible with effective ventilation at normal minute volumes. Because of these factors, it can be dangerous to put a patient with an acute severe asthma attack on a mechanical ventilator. The other side of this issue, of course, is that patients can die of respiratory failure and/or hypoxia thus one needs to know when the risks of respiratory failure exceed the risks of the treatment (ventilation). There are no absolute rules here but think about how respiratory failure results in death. The primary mechanism is hypoxia. Few patients die because their PaCO2 gets too high or because their pH gets too low. Hence, if adequate oxygenation can be maintained, there is still some time to direct therapy toward the underlying cause of respiratory failure, namely, the increased airway resistance. Again, all acute asthmatics should receive oxygen therapy. This buys time for other more definitive therapy to work. Watch for evidence of muscle fatigue and/or CO2 narcosis (which will eventually result in respiratory arrest). Typical signs are decreased respiratory effort in spite of increased loads, and altered mental status. My general method is to hold off on intubating an asthmatic until I'm unable to maintain adequate oxygenation or until the patient develops altered mental status (confusion, unresponsiveness, coma etc). Until these indicators are present, there is still time (though maybe not much time) to continue continuous inhaled beta-2 agonist therapy and steroids. Using this method I've had patients with CO2's transiently in the 90's stay awake and alert and wind up not needing the ventilator after another 15 minutes of aerosol therapy. This sort of approach, of course, requires constant monitoring by the physician at the bedside with frequent (if not continuous) assessment and re-assessment of the response to therapy.
After Intubation
Remember that as outlined above, intubation and mechanical ventilation are not a treatment for asthma but are only a treatment for respiratory failure and/or hypoxia. Once a patient is intubated, the treatment for asthma should be continued if not intensified with the use of continuous aerosolized bronchodilators and steroids, as well as IV steroids and optionally IV bronchodilators (usually Brethine (terbutaline)). The goals of mechanical ventilation in acute asthma are primarily to keep a patient alive while you wait on the asthma therapy to work, hopefully without killing the patient with the ventilator. Normal blood gasses are NOT the goal of mechanical ventilation in asthma. Adequate oxygenation with a minimum of barotrauma is the goal. It is frequently necessary to use very low respiratory rates (less than 6 breaths per minute in some cases) to avoid dangerous Auto-PEEP and its resultant sequelae. Patients, should in most cases, be pharmacologically sedated and paralyzed both to prevent dyssynchronous ventilation (bucking the vent) and to decrease the rate of metabolism and thus the requirement for ventilation and oxygenation. Fever should be treated to lower the metabolic rate if it is present. Auto-PEEP should be measured hourly initially and adjusted to a safe level (probably less than 10 in most patients though IV volume loading of the patient will make them more tolerant from a blood pressure stand-point). As Auto-PEEP decreases (signifying a reduced airway resistance) the respiratory rate can slowly be increased to correct the expected respiratory acidosis that most severe asthmatics on the ventilator will have when ventilated at low rates. Once breath sounds are clearing up, the continuous bronchodilator dosing can be made intermittent and sedation and paralysis can be weaned as can the ventilator itself in most cases. In most cases, mechanical ventilation will only be necessary for a few days (sometimes just a few hours will be adequate) though I've had some difficult cases require ventilation as long as two weeks with severe wheezing until right before weaning.
After Extubation
Patients who have been mechanically ventilated for asthma are in a very high risk group for mortality from asthma. They and their families should know this so they will take future attacks very seriously. They should be reminded that most asthma mortality occurs outside of the hospital and they should be very familiar with using a peak flow meter to monitor their progress.
References
Olsen GN: Asthma Concepts & Control in Olsen, GN: Basic Handouts in Pulmonary Medicine, 2/92.
Nowak RM, Pensler MI, Sarkar DD, et al. Comparison of peak expiratory flow and FEV1.0 admission criteria for acute bronchial asthma. Ann Emer Med 1982; 11:64-69.
Guidelines for the Diagnosis and Mangement of Asthma, National Heart, Lung, and Blood Institute, NIH, US Dept HHS, August 1991.
Miller TP: Identification, treatment of adults at increased risk of fatal asthma, Today in Medicine, Nov/Dec 1992.
Fish, JE: Status Asthmaticus in Current Therapy in Allergy, Immunology and Rheumatology.
Aerosol Therapy
December 05, 2009, 19:38 Filed in: Physics
Aerosol Therapy
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
An aerosol is a suspension of small particles of liquid or solid in a gas. The particles, synthetic or natural, fall within the size range of 0.005 to 50 in diameter. Those that are medically important are less than 3 in diameter. Gravity begins to lose its influence on particles at this mass size. Examples of aerosols include dusts, bacteria, yeast, water, and smoke.
Terminology
Stability of an aerosol is the ability to remain in suspension and maintain its integrity as an aerosol. Stability is dependent upon the size and nature of the particle, the concentration of particles, ambient humidity, and movement of the suspending gas. Instability is the propensity of a suspended particle to remove itself from suspension. For therapeutic aerosols, penetration refers to the depth to which an aerosol particle can be carried by a tidal breath. Deposition refers to the aerosol becoming unstable as particles rain-out or are retained within the respiratory tract. Clearance refers to removal of deposited particles by biologic mechanisms.
Aerosol Generation
There are two main types of aerosol generators in general clinical use today. They are jet nebulizers and ultrasonic nebulizers. A Jet nebulizer works by directing a high flow of gas over a capillary tube that is immersed into the fluid to be nebulized (made into an aerosol). The suction generated at the top of the capillary tube draws fluid up the tube and into the air. Particles of improper size (from a stability stand-point) are frequently directed against a baffle that will encourage rain-out such that the fluid to be nebulized is not wasted by the creation of unstable particles. The particles that rain-out fall back into the fluid reservoir so they can be nebulized again. Many nebulizers have an air intake or venturi to allow the entrainment of room air for dilution of the primary gas, usually oxygen.
An ultrasonic nebulizer consists of a power chamber and a nebulizing chamber. The power chamber includes a ceramic transducer that is described as piezoelectric because is changes electrical energy into pressure energy. The transducer vibrates at a very high frequency (that requires FCC certification) up to about 1.5 mHz. The transducer sits at the bottom of a water filled power chamber. The vibrational energy is transmitted through the water and focused on a flexible diaphragm that vibrates in sympathy. The diaphragm is in contact with the solution to be aerosolized and shakes the solution into particles. At low frequencies, waves are produced that may produce some larger aerosol particles. At high frequencies a fine mist is generated. At low power (amplitude) the particles are produced intermittently as waves break while at higher power settings the particles are liberated continuously. At very high power settings, the chemical makeup of some medications can be disrupted. Ultrasonic nebulizers tend to produce a more consistent particle size than do jet nebulizers and can produce very large volumes of respirable particles with much greater deposition into the lungs. There is some experimental evidence to suggest that long-term use of ultrasonic nebulization can result to disruption of surface tension stability in the lung, perhaps owing to the large amount of fluid deposited into the lungs. Ultrasonic nebulizers are limited in that they cannot aerosolize viscous solutions though this is not a problem clinically.
Aerosol Behavior
Once an aerosol is generated, there is initially quite a variety of particle sizes. As the aerosol ages, however, larger particles aggregate and become unstable, falling out of suspension. This results in a decrease in the size deviation of an aerosol such that the resulting aerosol tends to consist of particles close to 0.1 micron. The depth of penetration of an aerosol particle into the respiratory tract increases as the particle size decreases. The nose will completely filter particles down to 5 to 10 microns in diameter while particles of 1 micron and down can get past the upper airway and into the terminal alveoli. Particles of around 1 micron are retained in alveoli while particles much below this size do not deposit and are exhaled. The rate at which a particle will settle is related to physical properties such as gravity, mass, volume, density, and viscous resistance of air. For particles within the size range of 0.1 to 70 microns, the settling velocity of a particle is proportional to the product of its density and the square of its diameter: Settling rate = Density x Diameter squared. Particles, as they approach 0.1 micron in size, become almost molecular in character and are influenced greatly by the kinetic activity of the suspending gas to a greater extent than gravity. A smaller particle is actually kept in suspension by collisions with adjacent gas molecules as it has a high surface area to mass ratio compared to the larger, more massive particle which is more influenced by gravity. Below a given size (about 0.25 microns) particle deposition/retention is actually increased. Rain-out, or retention, of an aerosol can be facilitated by the inertia of a particle tending to keep the particle moving in a straight line when the flow of inspired air changes direction suddenly. Particles at the edge of a stream of gas are more likely to impact by this mechanism. Particle composition also influences particle stability. A hygroscopic particle will tend in accumulate water vapor and increase the size of itself while other particles might tend to dry out and decrease in size. This mechanism is influenced by the relative humidity of the suspending gas. Ventilatory patterns influence particle deposition and retention. Deposition and retention are directly related to inhaled tidal volume and inversely related to flow rate. These factors are only important in conducting airways and become less important as the inspired gas approaches the alveoli where there is little air movement. Aerosolized particles are cleared from the lung by means of ciliary mucus clearance and by means of pulmonary tissue clearance which is a combination of phagocytosis by macrophages and diffusion and dissolving into tissue fluids.
Medical Aerosols
The two main areas where aerosols are used therapeutically are for humidification therapy and medication delivery. Humidification therapy depends on both the bulk delivery of water or saline solutions to the airways and alveoli as well as the tendency of evaporating particles to increase the relative humidity of the suspending gas. Ultrasonic nebulizers, in particular, are very efficient at delivering large amounts of liquid to the respiratory tract. There is controversy regarding what fluid is best to deliver in this manner. Fluids that are very hypertonic or hypotonic tend to be irritating and lead to coughing and bronchospasm in susceptible individuals. The tonicity of aerosolized fluids also tends to change enroute to the alveoli depending on the humidity of the suspending gas. What starts out as an isotonic solution may be either hypertonic or hypotonic by the time it arrives as the site of deposition. There is also controversy as to whether delivery of liquids to the airways is of any therapeutic value in decreasing the viscosity of or increasing the clearance of mucus.
Medication Delivery
Aerosols are an attractive way to delivery drugs, particularly those whose site of action is the lungs themselves as relatively high doses are delivered to the site of action, sparing high systemic doses that might otherwise cause adverse systemic effects. Unfortunately, there are many problems with using aerosols to deliver medications to include inconsistent dose delivery, inadvertent gastrointestinal delivery, non-uniform distribution of medication in the lungs, and elicitation of bronchospasm. There are even those that theorize that the use of suspending gasses like fluorocarbons might be causing cardiac arrests secondary to cardiac toxicity in some asthmatics.
Dosage delivery
Aerosolized medications are inconsistently delivered to the patient. When one places a given amount of medication in a nebulizer, it is difficult, if not impossible, to predict how much of the medication will actually be delivered to the patient, much less to the site of action in the alveoli where it is theorized that most systemic absorption takes place. The initial site of lost medication is into the room as most aerosols are delivered without the benefit of a closed delivery system. Continuous aerosols such as those delivered by hand held, gas powered nebulizers deliver as much as 2/3 of their output during the patient's exhalation. Of the amount of aerosol produced during inspiration, some still leaks out of the mask or mouthpiece, some rains out in the nose and/or oropharynx and some is actually delivered to the lower airways and lungs. Metered dose inhalers are subject to many of the same limitations and those with very short ejection periods are even more susceptible to asynchronous delivery. Commercially available metered dose inhalers eject about 15cc of gas per actuation. Many text books recommend dosing aerosolized medications the way oral or parenteral medications are dosed, i.e. based on body weight. The problem with this is that patients of different sizes already have different deposition rates. For example, say you have a drug that you'd give to a patient at 1 mg/kg of body weight if given IV. If you are going to use a gas powered continuous nebulizer you would have to use at least 3 times this dose to just get the usual dose directed in the general direction of the patient during inspiration. Since deposition is also minute volume dependent, patients with smaller minute volumes (i.e. pediatric patients) will get less delivery of drug to the lungs than those with larger minute volumes. This means that if you put 2 mg of Terbutaline in a nebulizer for an adult that the same 2 mg of Terbutaline would give a proportionately smaller delivered dose to a newborn. Further complicating the picture is the fact that there is a greater tendency to trap the medication in the upper airway of an infant such that you really have to greatly increase the dose to the nebulizer to treat an infant so it might take 6 mg of Terbutaline in the nebulizer to give an infant the same dose per kg of body weight that an adult would receive with 2 mg of drug in the nebulizer. Basing the amount of medication you place in the nebulizer on the body weight of the patient in a linear fashion will not accurately predict dose delivery to the patient's lungs as they are really inversely related at best. Aerosolized medication dosing is further complicated by the variety of devices used to create the aerosol. There is no simple way to compare doses unless the same nebulizer is used. A case in point is the aerosolization of Pentamidine. There are plenty of recommendations as to what dose of medication to deliver but whatever dose you choose, you must use the same nebulizer used in the study you like or your dose delivery will be different than that which was recommended, perhaps more, perhaps less, perhaps not even close to what you thought you were delivering. Particle Size vs Site of delivery To further complicate matters, the particle size produced by various nebulizers, greatly influences where the aerosol will be deposited and also determines whether it will be retained or simply exhaled. Nebulizers are frequently called efficient if a large percentage of their delivered dose is retained but this usually means that they produce larger particles that are more likely to impact in the upper airway and not be delivered to the alveoli, if indeed, that is the intended target of delivery. In the case of Pentamidine, for example, it is recommended that the Respigard II be used. The retention of the 0.9 particles is only 5.3% meaning that only 5.3% of the dose from the nebulizer is retained. This sounds inefficient and is but if one of the other nebulizers were used then the particle size would result in more of the medication being delivered to airways instead of the alveoli where you want the medicine to go. Rain-out in airways is responsible for at least some of th e complications of therapy and is thus avoided by using a nebulizer producing smaller particles even if much of the aerosol is stable enough to be exhaled again. If one wanted to increase the delivered dose a rebreathing circuit could be used but this would increase the delivered dose to a level greater than what is recommended since the dosage recommendations are made assuming the intentional inefficiency of the the Respigard II.
Intubated patients
Nebulizers and metered dose inhalers have been used with intubated and mechanically ventilated patients. Factors influencing delivery include whether a continuous or inspiration-only nebulizer is used, where the nebulizer is placed in the circuit, and whether a nebulizer or a metered dose inhaler is used. Ventilator settings also influence drug delivery. In general, intubated patients will get less lung deposition and retention than non-intubated patients so dosing has to be adjusted accordingly. So what gives? If you've gotten the idea that it's a joke to pretend that medications can be precisely delivered by aerosol then you have the right idea. Given the many confounding factors influencing drug delivery, the only real ways to sensibly choose a dose is to use secondary indicators such as response to therapy (in the case of bronchodilators) or perhaps measurement of drug levels in serum or urine in the case of Pentamidine. Perhaps it would be more sensible if medications prepared for aerosol delivery were available in standard solutions with no particular dosage ordered and actual dose usage determined strictly on the basis of response.
References
Patel P, Mukai D, Wilson AF: Dose-response effects of two sizes of monodisperse isoproterenol in mild asthma. ARRD (1990 Feb) 141(2): 357-60.
Simonds AK, Newman SP, Johnson MA, Talaee N, Lee CA, Clarke SW: Alveolar targeting of aerosol pentamidine. Toward a rational delivery system. ARRD (1990 Apr) 141(4 Pt 1):827-9.
Kim CS, Trujillo D, Sackner MA: Size aspects of metered-dose inhaler aerosols. ARRD (1985 Jul) 132(1):137-42.
Ilowite JS, Baskin MI, Sheetz MS, Abd AG: Delivered dose and regional distribution of aerosolized pentamidine using different delivery systems. Chest (1991 May) 99(5):1139-44.
Hiller C, Mazumder M, Wilson D, Bone R: Aerodynamic size distribution of metered-dose bronchodilator aerosols. ARRD (1978 Aug) 118(2):311-7.
Peters JA: Humidity and Aerosol Therapy, in Spearman CB, Sheldon RL, Egan DF: Egan's Fundamentals of Respiratory Therapy, 4th edition, The C.V. Mosby Co., 1982.
Hess D, Daugherty A, Simmons M: The Volume of Gas Emitted from Metered Dose Inhalers, abstract, Resp Care, (1991 Nov), 36(11):1320.
ink JB, Cohen NH, Covington J, Mahlmeister MJ: Titration for Optimal Do se Response to Bronchodilators Using MDI and Spacer in Ventilated Adults, abstract, Resp Care, (1991 Nov), 36(11):1321.
Don Elton
Lexington, South Carolina
http://www.lexingtonpulmonary.com
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
An aerosol is a suspension of small particles of liquid or solid in a gas. The particles, synthetic or natural, fall within the size range of 0.005 to 50 in diameter. Those that are medically important are less than 3 in diameter. Gravity begins to lose its influence on particles at this mass size. Examples of aerosols include dusts, bacteria, yeast, water, and smoke.
Terminology
Stability of an aerosol is the ability to remain in suspension and maintain its integrity as an aerosol. Stability is dependent upon the size and nature of the particle, the concentration of particles, ambient humidity, and movement of the suspending gas. Instability is the propensity of a suspended particle to remove itself from suspension. For therapeutic aerosols, penetration refers to the depth to which an aerosol particle can be carried by a tidal breath. Deposition refers to the aerosol becoming unstable as particles rain-out or are retained within the respiratory tract. Clearance refers to removal of deposited particles by biologic mechanisms.
Aerosol Generation
There are two main types of aerosol generators in general clinical use today. They are jet nebulizers and ultrasonic nebulizers. A Jet nebulizer works by directing a high flow of gas over a capillary tube that is immersed into the fluid to be nebulized (made into an aerosol). The suction generated at the top of the capillary tube draws fluid up the tube and into the air. Particles of improper size (from a stability stand-point) are frequently directed against a baffle that will encourage rain-out such that the fluid to be nebulized is not wasted by the creation of unstable particles. The particles that rain-out fall back into the fluid reservoir so they can be nebulized again. Many nebulizers have an air intake or venturi to allow the entrainment of room air for dilution of the primary gas, usually oxygen.
An ultrasonic nebulizer consists of a power chamber and a nebulizing chamber. The power chamber includes a ceramic transducer that is described as piezoelectric because is changes electrical energy into pressure energy. The transducer vibrates at a very high frequency (that requires FCC certification) up to about 1.5 mHz. The transducer sits at the bottom of a water filled power chamber. The vibrational energy is transmitted through the water and focused on a flexible diaphragm that vibrates in sympathy. The diaphragm is in contact with the solution to be aerosolized and shakes the solution into particles. At low frequencies, waves are produced that may produce some larger aerosol particles. At high frequencies a fine mist is generated. At low power (amplitude) the particles are produced intermittently as waves break while at higher power settings the particles are liberated continuously. At very high power settings, the chemical makeup of some medications can be disrupted. Ultrasonic nebulizers tend to produce a more consistent particle size than do jet nebulizers and can produce very large volumes of respirable particles with much greater deposition into the lungs. There is some experimental evidence to suggest that long-term use of ultrasonic nebulization can result to disruption of surface tension stability in the lung, perhaps owing to the large amount of fluid deposited into the lungs. Ultrasonic nebulizers are limited in that they cannot aerosolize viscous solutions though this is not a problem clinically.
Aerosol Behavior
Once an aerosol is generated, there is initially quite a variety of particle sizes. As the aerosol ages, however, larger particles aggregate and become unstable, falling out of suspension. This results in a decrease in the size deviation of an aerosol such that the resulting aerosol tends to consist of particles close to 0.1 micron. The depth of penetration of an aerosol particle into the respiratory tract increases as the particle size decreases. The nose will completely filter particles down to 5 to 10 microns in diameter while particles of 1 micron and down can get past the upper airway and into the terminal alveoli. Particles of around 1 micron are retained in alveoli while particles much below this size do not deposit and are exhaled. The rate at which a particle will settle is related to physical properties such as gravity, mass, volume, density, and viscous resistance of air. For particles within the size range of 0.1 to 70 microns, the settling velocity of a particle is proportional to the product of its density and the square of its diameter: Settling rate = Density x Diameter squared. Particles, as they approach 0.1 micron in size, become almost molecular in character and are influenced greatly by the kinetic activity of the suspending gas to a greater extent than gravity. A smaller particle is actually kept in suspension by collisions with adjacent gas molecules as it has a high surface area to mass ratio compared to the larger, more massive particle which is more influenced by gravity. Below a given size (about 0.25 microns) particle deposition/retention is actually increased. Rain-out, or retention, of an aerosol can be facilitated by the inertia of a particle tending to keep the particle moving in a straight line when the flow of inspired air changes direction suddenly. Particles at the edge of a stream of gas are more likely to impact by this mechanism. Particle composition also influences particle stability. A hygroscopic particle will tend in accumulate water vapor and increase the size of itself while other particles might tend to dry out and decrease in size. This mechanism is influenced by the relative humidity of the suspending gas. Ventilatory patterns influence particle deposition and retention. Deposition and retention are directly related to inhaled tidal volume and inversely related to flow rate. These factors are only important in conducting airways and become less important as the inspired gas approaches the alveoli where there is little air movement. Aerosolized particles are cleared from the lung by means of ciliary mucus clearance and by means of pulmonary tissue clearance which is a combination of phagocytosis by macrophages and diffusion and dissolving into tissue fluids.
Medical Aerosols
The two main areas where aerosols are used therapeutically are for humidification therapy and medication delivery. Humidification therapy depends on both the bulk delivery of water or saline solutions to the airways and alveoli as well as the tendency of evaporating particles to increase the relative humidity of the suspending gas. Ultrasonic nebulizers, in particular, are very efficient at delivering large amounts of liquid to the respiratory tract. There is controversy regarding what fluid is best to deliver in this manner. Fluids that are very hypertonic or hypotonic tend to be irritating and lead to coughing and bronchospasm in susceptible individuals. The tonicity of aerosolized fluids also tends to change enroute to the alveoli depending on the humidity of the suspending gas. What starts out as an isotonic solution may be either hypertonic or hypotonic by the time it arrives as the site of deposition. There is also controversy as to whether delivery of liquids to the airways is of any therapeutic value in decreasing the viscosity of or increasing the clearance of mucus.
Medication Delivery
Aerosols are an attractive way to delivery drugs, particularly those whose site of action is the lungs themselves as relatively high doses are delivered to the site of action, sparing high systemic doses that might otherwise cause adverse systemic effects. Unfortunately, there are many problems with using aerosols to deliver medications to include inconsistent dose delivery, inadvertent gastrointestinal delivery, non-uniform distribution of medication in the lungs, and elicitation of bronchospasm. There are even those that theorize that the use of suspending gasses like fluorocarbons might be causing cardiac arrests secondary to cardiac toxicity in some asthmatics.
Dosage delivery
Aerosolized medications are inconsistently delivered to the patient. When one places a given amount of medication in a nebulizer, it is difficult, if not impossible, to predict how much of the medication will actually be delivered to the patient, much less to the site of action in the alveoli where it is theorized that most systemic absorption takes place. The initial site of lost medication is into the room as most aerosols are delivered without the benefit of a closed delivery system. Continuous aerosols such as those delivered by hand held, gas powered nebulizers deliver as much as 2/3 of their output during the patient's exhalation. Of the amount of aerosol produced during inspiration, some still leaks out of the mask or mouthpiece, some rains out in the nose and/or oropharynx and some is actually delivered to the lower airways and lungs. Metered dose inhalers are subject to many of the same limitations and those with very short ejection periods are even more susceptible to asynchronous delivery. Commercially available metered dose inhalers eject about 15cc of gas per actuation. Many text books recommend dosing aerosolized medications the way oral or parenteral medications are dosed, i.e. based on body weight. The problem with this is that patients of different sizes already have different deposition rates. For example, say you have a drug that you'd give to a patient at 1 mg/kg of body weight if given IV. If you are going to use a gas powered continuous nebulizer you would have to use at least 3 times this dose to just get the usual dose directed in the general direction of the patient during inspiration. Since deposition is also minute volume dependent, patients with smaller minute volumes (i.e. pediatric patients) will get less delivery of drug to the lungs than those with larger minute volumes. This means that if you put 2 mg of Terbutaline in a nebulizer for an adult that the same 2 mg of Terbutaline would give a proportionately smaller delivered dose to a newborn. Further complicating the picture is the fact that there is a greater tendency to trap the medication in the upper airway of an infant such that you really have to greatly increase the dose to the nebulizer to treat an infant so it might take 6 mg of Terbutaline in the nebulizer to give an infant the same dose per kg of body weight that an adult would receive with 2 mg of drug in the nebulizer. Basing the amount of medication you place in the nebulizer on the body weight of the patient in a linear fashion will not accurately predict dose delivery to the patient's lungs as they are really inversely related at best. Aerosolized medication dosing is further complicated by the variety of devices used to create the aerosol. There is no simple way to compare doses unless the same nebulizer is used. A case in point is the aerosolization of Pentamidine. There are plenty of recommendations as to what dose of medication to deliver but whatever dose you choose, you must use the same nebulizer used in the study you like or your dose delivery will be different than that which was recommended, perhaps more, perhaps less, perhaps not even close to what you thought you were delivering. Particle Size vs Site of delivery To further complicate matters, the particle size produced by various nebulizers, greatly influences where the aerosol will be deposited and also determines whether it will be retained or simply exhaled. Nebulizers are frequently called efficient if a large percentage of their delivered dose is retained but this usually means that they produce larger particles that are more likely to impact in the upper airway and not be delivered to the alveoli, if indeed, that is the intended target of delivery. In the case of Pentamidine, for example, it is recommended that the Respigard II be used. The retention of the 0.9 particles is only 5.3% meaning that only 5.3% of the dose from the nebulizer is retained. This sounds inefficient and is but if one of the other nebulizers were used then the particle size would result in more of the medication being delivered to airways instead of the alveoli where you want the medicine to go. Rain-out in airways is responsible for at least some of th e complications of therapy and is thus avoided by using a nebulizer producing smaller particles even if much of the aerosol is stable enough to be exhaled again. If one wanted to increase the delivered dose a rebreathing circuit could be used but this would increase the delivered dose to a level greater than what is recommended since the dosage recommendations are made assuming the intentional inefficiency of the the Respigard II.
Intubated patients
Nebulizers and metered dose inhalers have been used with intubated and mechanically ventilated patients. Factors influencing delivery include whether a continuous or inspiration-only nebulizer is used, where the nebulizer is placed in the circuit, and whether a nebulizer or a metered dose inhaler is used. Ventilator settings also influence drug delivery. In general, intubated patients will get less lung deposition and retention than non-intubated patients so dosing has to be adjusted accordingly. So what gives? If you've gotten the idea that it's a joke to pretend that medications can be precisely delivered by aerosol then you have the right idea. Given the many confounding factors influencing drug delivery, the only real ways to sensibly choose a dose is to use secondary indicators such as response to therapy (in the case of bronchodilators) or perhaps measurement of drug levels in serum or urine in the case of Pentamidine. Perhaps it would be more sensible if medications prepared for aerosol delivery were available in standard solutions with no particular dosage ordered and actual dose usage determined strictly on the basis of response.
References
Patel P, Mukai D, Wilson AF: Dose-response effects of two sizes of monodisperse isoproterenol in mild asthma. ARRD (1990 Feb) 141(2): 357-60.
Simonds AK, Newman SP, Johnson MA, Talaee N, Lee CA, Clarke SW: Alveolar targeting of aerosol pentamidine. Toward a rational delivery system. ARRD (1990 Apr) 141(4 Pt 1):827-9.
Kim CS, Trujillo D, Sackner MA: Size aspects of metered-dose inhaler aerosols. ARRD (1985 Jul) 132(1):137-42.
Ilowite JS, Baskin MI, Sheetz MS, Abd AG: Delivered dose and regional distribution of aerosolized pentamidine using different delivery systems. Chest (1991 May) 99(5):1139-44.
Hiller C, Mazumder M, Wilson D, Bone R: Aerodynamic size distribution of metered-dose bronchodilator aerosols. ARRD (1978 Aug) 118(2):311-7.
Peters JA: Humidity and Aerosol Therapy, in Spearman CB, Sheldon RL, Egan DF: Egan's Fundamentals of Respiratory Therapy, 4th edition, The C.V. Mosby Co., 1982.
Hess D, Daugherty A, Simmons M: The Volume of Gas Emitted from Metered Dose Inhalers, abstract, Resp Care, (1991 Nov), 36(11):1320.
ink JB, Cohen NH, Covington J, Mahlmeister MJ: Titration for Optimal Do se Response to Bronchodilators Using MDI and Spacer in Ventilated Adults, abstract, Resp Care, (1991 Nov), 36(11):1321.
Don Elton
Lexington, South Carolina
http://www.lexingtonpulmonary.com
Airway Emergencies
December 05, 2009, 19:38 Filed in: airway
Airway Emergencies
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
The airway, consisting either of natural anatomy or a plastic tube, is arguably the most important part of the pulmonary system. Without an adequate airway, the remainder of the cardiopulmonary system is of little value. Because of this importance, loss of patency becomes the most urgent emergency that can be imagined in medicine. Rapid accurate recognition and treatment of airway emergencies are essential to the provision of emergency and critical care medicine.
Anatomy
The natural human airway consists of the nasopharynx and oropharynx, the larynx, and the trachea. Most airway emergencies result from obstruction to airflow. Obstruction can result from internal obstruction either by edema, spasm, or a foreign body, or from external compression or distortion. Airway obstructions can be congenital or acquired. Examples of congenital airway obstructions are tracheal atresia, laryngeal web, choanal atresia, and vascular ring with tracheal compression. These congenital obstructions, if severe enough, can result in death in the delivery room if immediate surgical intervention is not provided.
Foreign Body Aspiration
Foreign body aspiration normally occurs during eating, particularly when the patient has an impaired gag reflex such as might be caused by consuming alcohol or by anatomical neurological deficits as might be seen following a stroke. With a complete obstruction, there is no sound of air movement audible at the mouth and the patient is unable to speak. Sternal, suprasternal, costal, and infracostal retractions are also common in upper airway obstruction as is a piston-like motion of the trachea as seen in the neck with inspiratory efforts. Of course, these findings are very temporary if the obstruction is not treated so airway obstruction must be assumed to exist in any apneic patient until proven otherwise. Treatment consists of either removing the obstruction via the fingers or instruments (forceps and laryngoscope for example) or by moving the obstruction below the level of the carina such that a complete obstruction only blocks ventilation to one lung. Complete obstruction can also be treated by bypassing the obstruction with a tracheotomy or cricothyrotomy. Some obstructions will require urgent bronchoscopy and the use of a rigid scope, if available, may be more successful given the larger channel size. The Heimlich maneuver may also be used when other more definitive methods are not immediately available. In cases of partial obstruction, one must be careful not to convert the situation to a complete obstruction and the urgency of treatment must be titrated to the degree of obstruction with severe partial obstructions being treated like complete obstructions. One seldom available technique for buying time in cases of partial airway obstruction is the use of a helium-oxygen mixture since the helium has a lower density than nitrogen and thus can ventilate a patient with less pressure required. If a patient must be ventilated past a partial airway obstruction, the ventilation should be provided by a manual resuscitator instead of a mechanical ventilator and slow deep breaths should be delivered with attention given to providing adequate expiratory time. Using a manual resuscitator allows for immediate detection of changes in airway resistance and will tend to do a better job of ventilating the patient.
Angioedema
Angioedema is an allergic type reaction that results in any combination of lip, face, neck, tongue, uvula, palate, epiglootic, glottic, and tracheal edema. The most common causes are drugs (particular ACE inhibitors - angiotensin converting enzyme inhibitor antihypertensive medications like Vasotec (enalapril), Capoten (captopril) and others). Other causes include various foods (commonly shellfish), and an ideopathic form (hereditary angioedema). This problem is a little tricky as it may occur after months or even years of incident free use of ACE inhibitor drugs. Most cases present with painless lip swelling, sometimes one, sometimes both. Symptoms increase if exposure to the offending agent continues and this is common since the cause is frequently unsuspected by the patient since it may not be a new exposure. If there is swelling of anything inside the mouth or throat then airway obstruction can occur leading to death. Intubation via the oral route is frequently impossible and may be difficult via the nasal route as well. Once airway obstruction has reached a critical stage, manipulation of the airway could lead to worsening edema and lead to complete obstruction. Ideally a patient with angioedema should be intubated in the operating room with someone ready to perform an emergent tracheotomy or cricothyrotomy if needed. Patients with swelling of the lip, uvual, or who already have respiratory compromise need admission and anyone who has difficulty breathing, swallowing, or speaking should have an airway secured as soon as safely feasible. Other treatments include subcutaneous epinephrine (when not otherwise contraindicated), steroids, Benadryl (diphenhydramine), and histamine blocker anti-acid medications like Tagamet (cimetidine) etc. Recovery usually occurs within a few days provided the causative substance is removed.
Infectious airway obstruction
The two most common infectious causes of airway obstruction are laryngotracheobronchitis (croup) and epiglottitis. Both are more common in children but both can occur in adults. Croup is usually a viral illness that results in subglottic (tracheal) stenosis.. The onset is usually over 4-5 days at the end of an upper respiratory infection. Croup does not usually become life threatening but it can be if severe. Diagnosis can be made by a PA soft tissue neck x-ray which will show tracheal narrowing at the top of the tracheal air shadow (steeple sign). Patients with croup have a variable amount of respiratory distress and have a peculiar barking cough (at least infants do). Croup is normally treated with cool mist and sometimes steroids and/or aerosolized racemic epinephrine which acts as a topical vasoconstrictor. The most important thing to remember with croup is that you must be sure that the patient doesn't really have epiglottitis which is usually a more serious condition. Epiglottis usually results from a bacterial infection, frequently Haemophilus influenzae. The onset is rapid and can progress to severe airway obstruction within 6-8 hours in infants though usually it takes longer in adults. Stridor, dysphagia, odynophagia, and drooling (from inability to swallow) are typical symptoms. Patients with epiglottitis tend to be very anxious (not to mention their doctors). A lateral soft tissue neck x-ray is usually diagnostic but if obstruction is severe the patient should probably proceed to the operating suite for a controlled intubation by the most experienced person available rather than risking a complete airway obstruction in the radiology department. Laryngoscopy should ideally not be attempted unless personnel and equipment for an emergent tracheotomy is available. An abscess can also obstruct the upper airway. Symptoms may vary depending on the location but are usually similar to those of epiglottitis. Again, a lateral soft-tissue neck x-ray is helpful for diagnosis and a CT scan is useful if the airway can be protected.
Airway Trauma
Airway trauma can result from either blunt or penetrating injuries. Blunt trauma can cause a collapse of the trachea with intraluminal obstruction from the extrinsic pressure or there can be disruption of the trachea or major bronchi resulting in air leaks. Air leaks from the major airways can result in soft tissue and subcutaneous emphysema which can either be benign or can compress the airway or cause a pneumothorax or pneumomediastinum. If the history of injury suggests blunt or penetrating trauma to the chest or neck, then the soft tissues should be palpated for deformities or subcutaneous air and x-rays should be obtained to look for evidence of air leaks. Positive pressure applied to the airway should be avoided if possible or at least minimized to prevent the extension of air leaks that might otherwise be self limited.
Artificial airway emergencies
Artificial airways are normally tracheostomy tubes, and oral/nasal endotracheal tubes. Other airways would be tracheal buttons and the like. It is important that physicians caring for patients with artificial airways be very familiar with the construction and proper use of those airways as improper use can be life threatening. For example, it's a bad idea to inflate the cuff of a fenestrated tracheostomy tube when you have both the external and internal lumens occluded. Endotracheal tubes can become obstructed with mucus, particularly in cases where the mucus contains blood, secretions are thick, humidification is inadequate, and/or airways are small in diameter or have sharp bends that narrow the lumen. It is possible to have an endotracheal tube totally obstructed by mucus that a patient cannot breath around and yet be able to pass a section catheter through the viscid obstruction. Sometimes a partial obstruction of an endotracheal tube will cause musical breath sounds over the trachea. In mechanically ventilated patients you might note adequate breath sounds for mechanical breaths (albeit with high peak pressures) but note no air movement with weaker spontaneous efforts. If there is any doubt of airway patency then the airway should be replaced immediately. It is possible for an airway cuff, if overinflated or defective, to herniate over the end of the tube resulting in partial or total airway obstruction. If this happens the airway should be replaced as a cuff deformed in this way may be more likely to herniate again. Cuff trauma to the tracheal mucosa can result in edema and/or fibrotic scarring that will obstruct the trachea upon extubation. This will not usually be suspected until the patient develops respiratory distress upon extubation. For this reason, patients should never be extubated unless someone is present who can immediately reinsert an endotracheal tube, perhaps of a smaller diameter than the one removed. With longer term intubation, it is possible for a cuff to erode through the tracheal wall and into blood vessels. This is less common today with lower pressure cuffs but can still happen. Usually airway obstruction secondary to the bleeding is more important than the amount of blood loss so the initial goal of therapy is to protect the airway, usually by inserting the tube beyond the point of bleeding and inflating the cuff. Elevating the head of the bed will reduce the blood pressure in the bleeding vessel until surgical assistance is available. Cuffs that won't hold their air pressure usually result from leaks somewhere between the cuff itself and the syringe adapter. Cuffs frequently can be torn by teeth or nasal bones and tubes have to be replaced when this happens. If the leak is in the pilot line valve (where the syringe attaches) or the pilot line is accidentally cut you can try inserting a stop-cock where the syringe goes or alternatively can cut the pilot line and insert a blunt needle with a stop-cock attached to replace the valve that came with the tube.
Accidental Extubation
This can be an emergency if there is difficulty replacing the airway or if it just isn't detected in a reasonable amount of time. Everyone knows to listen for breath sounds to verify an endotracheal tube's position but many don't realize that you can get pretty good breath sounds with the endotracheal tube cuff above the vocal cords or even in the esophagus. Two fairly reliable signs of an extubated patient are the patient's ability to speak or large leaks of ventilator breaths around a properly inflated tube. One quick reliable method of verifying that a tube is in the trachea is to just use a laryngoscope to look at the tube going beyond the cords. An alternative but less desirable method is to get a PA and lateral chest x-ray. The lateral is most important as the trachea is an anterior structure while the esophagus is posterior. In the patient with a tracheostomy, particularly a fresh tracheostomy, there is a possibility that it will be difficult to find the stoma in the neck through which to replace an accidentally removed tube. Remember that most such patients still have lips through which you can pass an oral tracheal tube in an emergency. Also, remember that you can always use a plain endotracheal tube to replace a tracheostomy tube in cases where the proper size tracheostomy tube isn't available or where the upper airway has been damaged by trauma, infection, or is bleeding. Several years ago I saw a patient who had fallen on a running chain saw and had severed his trachea and esophagus. A paramedic at the scene saved his life by intubating the free end of his trachea with an endotracheal tube.
References
Elton DR, Berkowitz GP: Endotracheal tube obstruction in neonates, Perinatology-Neonatology, 5:5, pp 75-80, 1981.
Shapiro BA, Harrison RA, Trout CA: Airway care in Clinical Application of Respiratory Care, , 2nd ed., Year Book Medical Publishers, 1979.
Rowe LD: Otolaryngology in Way LW: Current Surgical Diagnosis & Treatment, Lange Medical Publications, 1981.
Don Elton delton@lexpcc.net
Lexington, South Carolina
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
The airway, consisting either of natural anatomy or a plastic tube, is arguably the most important part of the pulmonary system. Without an adequate airway, the remainder of the cardiopulmonary system is of little value. Because of this importance, loss of patency becomes the most urgent emergency that can be imagined in medicine. Rapid accurate recognition and treatment of airway emergencies are essential to the provision of emergency and critical care medicine.
Anatomy
The natural human airway consists of the nasopharynx and oropharynx, the larynx, and the trachea. Most airway emergencies result from obstruction to airflow. Obstruction can result from internal obstruction either by edema, spasm, or a foreign body, or from external compression or distortion. Airway obstructions can be congenital or acquired. Examples of congenital airway obstructions are tracheal atresia, laryngeal web, choanal atresia, and vascular ring with tracheal compression. These congenital obstructions, if severe enough, can result in death in the delivery room if immediate surgical intervention is not provided.
Foreign Body Aspiration
Foreign body aspiration normally occurs during eating, particularly when the patient has an impaired gag reflex such as might be caused by consuming alcohol or by anatomical neurological deficits as might be seen following a stroke. With a complete obstruction, there is no sound of air movement audible at the mouth and the patient is unable to speak. Sternal, suprasternal, costal, and infracostal retractions are also common in upper airway obstruction as is a piston-like motion of the trachea as seen in the neck with inspiratory efforts. Of course, these findings are very temporary if the obstruction is not treated so airway obstruction must be assumed to exist in any apneic patient until proven otherwise. Treatment consists of either removing the obstruction via the fingers or instruments (forceps and laryngoscope for example) or by moving the obstruction below the level of the carina such that a complete obstruction only blocks ventilation to one lung. Complete obstruction can also be treated by bypassing the obstruction with a tracheotomy or cricothyrotomy. Some obstructions will require urgent bronchoscopy and the use of a rigid scope, if available, may be more successful given the larger channel size. The Heimlich maneuver may also be used when other more definitive methods are not immediately available. In cases of partial obstruction, one must be careful not to convert the situation to a complete obstruction and the urgency of treatment must be titrated to the degree of obstruction with severe partial obstructions being treated like complete obstructions. One seldom available technique for buying time in cases of partial airway obstruction is the use of a helium-oxygen mixture since the helium has a lower density than nitrogen and thus can ventilate a patient with less pressure required. If a patient must be ventilated past a partial airway obstruction, the ventilation should be provided by a manual resuscitator instead of a mechanical ventilator and slow deep breaths should be delivered with attention given to providing adequate expiratory time. Using a manual resuscitator allows for immediate detection of changes in airway resistance and will tend to do a better job of ventilating the patient.
Angioedema
Angioedema is an allergic type reaction that results in any combination of lip, face, neck, tongue, uvula, palate, epiglootic, glottic, and tracheal edema. The most common causes are drugs (particular ACE inhibitors - angiotensin converting enzyme inhibitor antihypertensive medications like Vasotec (enalapril), Capoten (captopril) and others). Other causes include various foods (commonly shellfish), and an ideopathic form (hereditary angioedema). This problem is a little tricky as it may occur after months or even years of incident free use of ACE inhibitor drugs. Most cases present with painless lip swelling, sometimes one, sometimes both. Symptoms increase if exposure to the offending agent continues and this is common since the cause is frequently unsuspected by the patient since it may not be a new exposure. If there is swelling of anything inside the mouth or throat then airway obstruction can occur leading to death. Intubation via the oral route is frequently impossible and may be difficult via the nasal route as well. Once airway obstruction has reached a critical stage, manipulation of the airway could lead to worsening edema and lead to complete obstruction. Ideally a patient with angioedema should be intubated in the operating room with someone ready to perform an emergent tracheotomy or cricothyrotomy if needed. Patients with swelling of the lip, uvual, or who already have respiratory compromise need admission and anyone who has difficulty breathing, swallowing, or speaking should have an airway secured as soon as safely feasible. Other treatments include subcutaneous epinephrine (when not otherwise contraindicated), steroids, Benadryl (diphenhydramine), and histamine blocker anti-acid medications like Tagamet (cimetidine) etc. Recovery usually occurs within a few days provided the causative substance is removed.
Infectious airway obstruction
The two most common infectious causes of airway obstruction are laryngotracheobronchitis (croup) and epiglottitis. Both are more common in children but both can occur in adults. Croup is usually a viral illness that results in subglottic (tracheal) stenosis.. The onset is usually over 4-5 days at the end of an upper respiratory infection. Croup does not usually become life threatening but it can be if severe. Diagnosis can be made by a PA soft tissue neck x-ray which will show tracheal narrowing at the top of the tracheal air shadow (steeple sign). Patients with croup have a variable amount of respiratory distress and have a peculiar barking cough (at least infants do). Croup is normally treated with cool mist and sometimes steroids and/or aerosolized racemic epinephrine which acts as a topical vasoconstrictor. The most important thing to remember with croup is that you must be sure that the patient doesn't really have epiglottitis which is usually a more serious condition. Epiglottis usually results from a bacterial infection, frequently Haemophilus influenzae. The onset is rapid and can progress to severe airway obstruction within 6-8 hours in infants though usually it takes longer in adults. Stridor, dysphagia, odynophagia, and drooling (from inability to swallow) are typical symptoms. Patients with epiglottitis tend to be very anxious (not to mention their doctors). A lateral soft tissue neck x-ray is usually diagnostic but if obstruction is severe the patient should probably proceed to the operating suite for a controlled intubation by the most experienced person available rather than risking a complete airway obstruction in the radiology department. Laryngoscopy should ideally not be attempted unless personnel and equipment for an emergent tracheotomy is available. An abscess can also obstruct the upper airway. Symptoms may vary depending on the location but are usually similar to those of epiglottitis. Again, a lateral soft-tissue neck x-ray is helpful for diagnosis and a CT scan is useful if the airway can be protected.
Airway Trauma
Airway trauma can result from either blunt or penetrating injuries. Blunt trauma can cause a collapse of the trachea with intraluminal obstruction from the extrinsic pressure or there can be disruption of the trachea or major bronchi resulting in air leaks. Air leaks from the major airways can result in soft tissue and subcutaneous emphysema which can either be benign or can compress the airway or cause a pneumothorax or pneumomediastinum. If the history of injury suggests blunt or penetrating trauma to the chest or neck, then the soft tissues should be palpated for deformities or subcutaneous air and x-rays should be obtained to look for evidence of air leaks. Positive pressure applied to the airway should be avoided if possible or at least minimized to prevent the extension of air leaks that might otherwise be self limited.
Artificial airway emergencies
Artificial airways are normally tracheostomy tubes, and oral/nasal endotracheal tubes. Other airways would be tracheal buttons and the like. It is important that physicians caring for patients with artificial airways be very familiar with the construction and proper use of those airways as improper use can be life threatening. For example, it's a bad idea to inflate the cuff of a fenestrated tracheostomy tube when you have both the external and internal lumens occluded. Endotracheal tubes can become obstructed with mucus, particularly in cases where the mucus contains blood, secretions are thick, humidification is inadequate, and/or airways are small in diameter or have sharp bends that narrow the lumen. It is possible to have an endotracheal tube totally obstructed by mucus that a patient cannot breath around and yet be able to pass a section catheter through the viscid obstruction. Sometimes a partial obstruction of an endotracheal tube will cause musical breath sounds over the trachea. In mechanically ventilated patients you might note adequate breath sounds for mechanical breaths (albeit with high peak pressures) but note no air movement with weaker spontaneous efforts. If there is any doubt of airway patency then the airway should be replaced immediately. It is possible for an airway cuff, if overinflated or defective, to herniate over the end of the tube resulting in partial or total airway obstruction. If this happens the airway should be replaced as a cuff deformed in this way may be more likely to herniate again. Cuff trauma to the tracheal mucosa can result in edema and/or fibrotic scarring that will obstruct the trachea upon extubation. This will not usually be suspected until the patient develops respiratory distress upon extubation. For this reason, patients should never be extubated unless someone is present who can immediately reinsert an endotracheal tube, perhaps of a smaller diameter than the one removed. With longer term intubation, it is possible for a cuff to erode through the tracheal wall and into blood vessels. This is less common today with lower pressure cuffs but can still happen. Usually airway obstruction secondary to the bleeding is more important than the amount of blood loss so the initial goal of therapy is to protect the airway, usually by inserting the tube beyond the point of bleeding and inflating the cuff. Elevating the head of the bed will reduce the blood pressure in the bleeding vessel until surgical assistance is available. Cuffs that won't hold their air pressure usually result from leaks somewhere between the cuff itself and the syringe adapter. Cuffs frequently can be torn by teeth or nasal bones and tubes have to be replaced when this happens. If the leak is in the pilot line valve (where the syringe attaches) or the pilot line is accidentally cut you can try inserting a stop-cock where the syringe goes or alternatively can cut the pilot line and insert a blunt needle with a stop-cock attached to replace the valve that came with the tube.
Accidental Extubation
This can be an emergency if there is difficulty replacing the airway or if it just isn't detected in a reasonable amount of time. Everyone knows to listen for breath sounds to verify an endotracheal tube's position but many don't realize that you can get pretty good breath sounds with the endotracheal tube cuff above the vocal cords or even in the esophagus. Two fairly reliable signs of an extubated patient are the patient's ability to speak or large leaks of ventilator breaths around a properly inflated tube. One quick reliable method of verifying that a tube is in the trachea is to just use a laryngoscope to look at the tube going beyond the cords. An alternative but less desirable method is to get a PA and lateral chest x-ray. The lateral is most important as the trachea is an anterior structure while the esophagus is posterior. In the patient with a tracheostomy, particularly a fresh tracheostomy, there is a possibility that it will be difficult to find the stoma in the neck through which to replace an accidentally removed tube. Remember that most such patients still have lips through which you can pass an oral tracheal tube in an emergency. Also, remember that you can always use a plain endotracheal tube to replace a tracheostomy tube in cases where the proper size tracheostomy tube isn't available or where the upper airway has been damaged by trauma, infection, or is bleeding. Several years ago I saw a patient who had fallen on a running chain saw and had severed his trachea and esophagus. A paramedic at the scene saved his life by intubating the free end of his trachea with an endotracheal tube.
References
Elton DR, Berkowitz GP: Endotracheal tube obstruction in neonates, Perinatology-Neonatology, 5:5, pp 75-80, 1981.
Shapiro BA, Harrison RA, Trout CA: Airway care in Clinical Application of Respiratory Care, , 2nd ed., Year Book Medical Publishers, 1979.
Rowe LD: Otolaryngology in Way LW: Current Surgical Diagnosis & Treatment, Lange Medical Publications, 1981.
Don Elton delton@lexpcc.net
Lexington, South Carolina