- Email: [email protected]
Pitfalls in salicylate toxicity
Correspondence Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol 2006;48:931-8. [3] Lotrionte M, Biondi-Zoccai GG, Agostoni P, et al. Meta-analysis appraising high clopidogrel loading in patients undergoing percutaneous coronary intervention. Am J Cardiol 2007;100:1199-206. [4] De Luca G, Suryapranata H, Stone GW, et al. Relationship between patient's risk profile and benefits in mortality from adjunctive abciximab to mechanical revascularization for ST-segment elevation myocardial infarction: a meta-regression analysis of randomized trials. J Am Coll Cardiol 2006;47:685-6. [5] Chen KY, Rha SW, Li YJ, et al. Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 2009;119:3207-14.
Pitfalls in salicylate toxicity To the Editor, We read with great interest the report by Drs Herres, Ryan, and Salzman entitled “Delayed Salicylate Toxicity With Undetectable Initial Levels After Large-dose Aspirin Ingestion” [1]. The authors have uncovered many of the pitfalls that have plagued treatment of aspirin-poisoned patients and make it such a difficult ingestion to treat appropriately. It also brings home the point that salicylate intoxication, like acetaminophen, may seem relatively innocuous in the face of worsening toxicity. One of the conclusions is that patients who ingest large quantities of aspirin may be at risk for delayed toxicity. The potential for delayed toxicity is related to many factors and has been well described [2,3]. Absorption may be delayed due to salicylate-induced gastric pylorospasm, bezoar formation, or sustained release or enteric product formulation. Distribution is largely related to the patient's serum protein, and because protein binding is saturated, the unbound fractions increase rapidly. In addition, distribution is related to the patient's serum pH. The lower the pH, the more nonionized salicylate is available to freely cross membranes and the higher the volume of distribution becomes. Elimination is affected by multiple mechanisms including hepatic metabolism, level of dehydration, and pH. Most of the 5 major elimination routes can be saturated with respect to their kinetics and which quickly leads to zero-order elimination kinetics and prolonged elimination rates. The initial laboratory level of “undetectable” probably represents a level that was not zero but rather below the cutoff value for reporting from their laboratory. In most laboratories, that is a salicylate level of 10 mg/dL. However, supporting laboratory data suggests that he was already salicylate toxic because he had an anion gap of 17. In this case, the “normal” serum bicarbonate was confusing because the gap already showed unmeasured anions. His arterial blood gas (ABG) also documented a marked respiratory alkalosis with a metabolic acidosis (pH should have been 7.50 with a PCO2 of 27 mm Hg). Three hours after ingestion,
383 he had a salicylate level of 33 mg/dL. Ideally, this level should have been accompanied by a repeat set of electrolytes and ABG, but if you evaluate this level with the earlier pH and HCO3, the patient already significantly toxic because he had progressed passed a pure respiratory alkalosis. A repeat level of 35 mg/dL at 7 hours suggests that although he was eliminating some of the drug, he continued to absorb more than he was eliminating. By the time the patient returned with a salicylate level of 128 mg/dL, he had deteriorated into both a metabolic and a respiratory acidosis. Salicylate intoxication may seem innocuous unless you look for the subtle findings. Although the authors report an initial respiratory rate of 18, there is no mention of the depth of breathing. Hyperpnea [4] commonly occurs in salicylate-intoxicated patients instead of tachypnea but is missed unless specific attention is paid. These patients have extremely large minute ventilation, which must be appreciated. Intubation is a classic point where these patients rapidly deteriorate. Paralyzing patients for rapid sequence intubation leads to a sudden loss of respiratory compensation for the acidosis and a precipitous fall in pH. After intubation, it is unfortunately too common to reflexively set the vent with a normal rate and tidal volume. When the patient returned from the Crisis Response Center, there is a documented respiratory rate of 20 breaths/min, but again, we do not know the depth of these breaths. At the time of intubation, this patient, despite what seems to be a normal PCO2, was in respiratory failure based on his entire acid-base picture and needed to have his minute ventilation exceeded. Once the patient becomes acidotic, the nonionized salicylate rapidly crosses the blood brain barrier where it can cause central nervous system acidosis leading to cerebral edema and seizures. If the patient seizes, the pH lowers further leading to a rapid decline and death. This article reinforces several crucial points in the treatment of salicylate intoxication: (1) carefully examine your aspirin-poisoned patient's breathing and note the depth of respiration in addition to respiratory rate; (2) interpret laboratory data in conjunction with the clinical setting; (3) understand the limitations of your blood tests, particularly the toxicology testing; (4) when you intubate an acidotic patient who is breathing on his own, you should match or exceed his intrinsic minute ventilation and then check an ABG immediately afterward so that you do not miss the loss of respiratory compensation; finally (5), consider getting expert help even if the ingestion seems to be relatively benign at presentation. Keenan Bora MD Cynthia Aaron MD Regional Poison Center of Michigan at Children's Hospital of Michigan Detroit, MI 48201, USA doi:10.1016/j.ajem.2009.12.003
384
References [1] Herres J, Ryan D, Salzman M. Delayed salicylate toxicity with undetectable initial levels after large-dose aspirin ingestion. Am J Emerg Med 2009;27(9):1173.e1-e3. [2] Levy G. Clinical pharmacokinetics of aspirin. Pediatrics 1978;62 (Suppl):867-72. [3] O'Malley GF. Emergency department management of the salicylatepoisoned patient. Emerg Med Clin North Am 2007;25(2):333-46. [4] Temple AR. Acute and chronic effects of aspirin toxicity and their treatment. Arch Intern Med 1981;141:364-9.
Prehospital physician management of pericardial tamponade due to penetrating trauma
Correspondence recommend consideration of this technique that is straightforward for the nonsurgeon to learn and to perform [5]. Although we would also question in this case the appropriateness of massive fluid resuscitation and the requirement for rapid sequence induction of anesthesia in an already apneic patient, we believe the delay of 62 minutes between first medical contact and surgical relief of tamponade might have been significantly reduced by a more focused and surgically aggressive approach. The discussion of hypercarbia's relationship to pericardial pressure based on research in dogs is interesting but, in our view, is a distraction from the practical considerations of managing the patient in extremis with penetrating truncal trauma.
To the Editor, Dr Barthélémy and colleagues' interesting case report demonstrates the importance of the identification of pericardial tamponade, the utility of ultrasound, and the possibility of excellent outcome in patients with tamponade due to a right ventricular stab wound who receive timely surgical intervention [1]. The European model of physician-based prehospital critical care remains under skeptical scrutiny in other parts of the world, and we wish to highlight that a very different and more definitive approach to pericardial tamponade due to penetrating injury would be pursued in some other physician-based systems. The authors note that they did not perform pericardiocentesis because of a lack of experience of the technique and the belief that it may be time-consuming, while also conceding that it may be futile without surgical control of the underlying cardiac wound. Impressive survival rates from prehospital clamshell thoracotomy with cardiac wound control are well documented [2], which has become established practice in a number of physician-staffed prehospital services [3,4]. We would
Cliff Reid BM Karel Habig MB BS Greater Sydney Area Helicopter Emergency Medical Service Ambulance Service of New South Wales Sydney, Australia doi:10.1016/j.ajem.2009.12.021
References [1] Barthélémy R, Bounes V, Minville V, Houze-Cerfon C, Ducasse J. Prehospital mechanical ventilation of a critical cardiac tamponade. Am J Emerg Med 2009;27:1020.e1-e3. [2] Coats TJ, Keogh S, Clark H, et al. Prehospital resuscitative thoracotomy for cardiac arrest after penetrating trauma: rationale and case series. J Trauma 2001;50(4):670-3. [3] Deakin CD. From agonal to output: an ECG history of a successful prehospital thoracotomy. Resuscitation 2007;75(3):525-9. [4] Corral E, Silva J, Suárez RM, Nuñez J, Cuesta C. A successful emergency thoracotomy performed in the field. Resuscitation 2007;75 (3):530-3. [5] Wise D, Davies G, Lockey D, Coats T, Hyde J, Goode P. Thoracotomy: how to do it. Emerg Med J 2005;22(1):22-4.
Pitfalls in salicylate toxicity To the Editor, We read with great interest the report by Drs Herres, Ryan, and Salzman entitled “Delayed Salicylate Toxicity With Undetectable Initial Levels After Large-dose Aspirin Ingestion” [1]. The authors have uncovered many of the pitfalls that have plagued treatment of aspirin-poisoned patients and make it such a difficult ingestion to treat appropriately. It also brings home the point that salicylate intoxication, like acetaminophen, may seem relatively innocuous in the face of worsening toxicity. One of the conclusions is that patients who ingest large quantities of aspirin may be at risk for delayed toxicity. The potential for delayed toxicity is related to many factors and has been well described [2,3]. Absorption may be delayed due to salicylate-induced gastric pylorospasm, bezoar formation, or sustained release or enteric product formulation. Distribution is largely related to the patient's serum protein, and because protein binding is saturated, the unbound fractions increase rapidly. In addition, distribution is related to the patient's serum pH. The lower the pH, the more nonionized salicylate is available to freely cross membranes and the higher the volume of distribution becomes. Elimination is affected by multiple mechanisms including hepatic metabolism, level of dehydration, and pH. Most of the 5 major elimination routes can be saturated with respect to their kinetics and which quickly leads to zero-order elimination kinetics and prolonged elimination rates. The initial laboratory level of “undetectable” probably represents a level that was not zero but rather below the cutoff value for reporting from their laboratory. In most laboratories, that is a salicylate level of 10 mg/dL. However, supporting laboratory data suggests that he was already salicylate toxic because he had an anion gap of 17. In this case, the “normal” serum bicarbonate was confusing because the gap already showed unmeasured anions. His arterial blood gas (ABG) also documented a marked respiratory alkalosis with a metabolic acidosis (pH should have been 7.50 with a PCO2 of 27 mm Hg). Three hours after ingestion,
383 he had a salicylate level of 33 mg/dL. Ideally, this level should have been accompanied by a repeat set of electrolytes and ABG, but if you evaluate this level with the earlier pH and HCO3, the patient already significantly toxic because he had progressed passed a pure respiratory alkalosis. A repeat level of 35 mg/dL at 7 hours suggests that although he was eliminating some of the drug, he continued to absorb more than he was eliminating. By the time the patient returned with a salicylate level of 128 mg/dL, he had deteriorated into both a metabolic and a respiratory acidosis. Salicylate intoxication may seem innocuous unless you look for the subtle findings. Although the authors report an initial respiratory rate of 18, there is no mention of the depth of breathing. Hyperpnea [4] commonly occurs in salicylate-intoxicated patients instead of tachypnea but is missed unless specific attention is paid. These patients have extremely large minute ventilation, which must be appreciated. Intubation is a classic point where these patients rapidly deteriorate. Paralyzing patients for rapid sequence intubation leads to a sudden loss of respiratory compensation for the acidosis and a precipitous fall in pH. After intubation, it is unfortunately too common to reflexively set the vent with a normal rate and tidal volume. When the patient returned from the Crisis Response Center, there is a documented respiratory rate of 20 breaths/min, but again, we do not know the depth of these breaths. At the time of intubation, this patient, despite what seems to be a normal PCO2, was in respiratory failure based on his entire acid-base picture and needed to have his minute ventilation exceeded. Once the patient becomes acidotic, the nonionized salicylate rapidly crosses the blood brain barrier where it can cause central nervous system acidosis leading to cerebral edema and seizures. If the patient seizes, the pH lowers further leading to a rapid decline and death. This article reinforces several crucial points in the treatment of salicylate intoxication: (1) carefully examine your aspirin-poisoned patient's breathing and note the depth of respiration in addition to respiratory rate; (2) interpret laboratory data in conjunction with the clinical setting; (3) understand the limitations of your blood tests, particularly the toxicology testing; (4) when you intubate an acidotic patient who is breathing on his own, you should match or exceed his intrinsic minute ventilation and then check an ABG immediately afterward so that you do not miss the loss of respiratory compensation; finally (5), consider getting expert help even if the ingestion seems to be relatively benign at presentation. Keenan Bora MD Cynthia Aaron MD Regional Poison Center of Michigan at Children's Hospital of Michigan Detroit, MI 48201, USA doi:10.1016/j.ajem.2009.12.003
384
References [1] Herres J, Ryan D, Salzman M. Delayed salicylate toxicity with undetectable initial levels after large-dose aspirin ingestion. Am J Emerg Med 2009;27(9):1173.e1-e3. [2] Levy G. Clinical pharmacokinetics of aspirin. Pediatrics 1978;62 (Suppl):867-72. [3] O'Malley GF. Emergency department management of the salicylatepoisoned patient. Emerg Med Clin North Am 2007;25(2):333-46. [4] Temple AR. Acute and chronic effects of aspirin toxicity and their treatment. Arch Intern Med 1981;141:364-9.
Prehospital physician management of pericardial tamponade due to penetrating trauma
Correspondence recommend consideration of this technique that is straightforward for the nonsurgeon to learn and to perform [5]. Although we would also question in this case the appropriateness of massive fluid resuscitation and the requirement for rapid sequence induction of anesthesia in an already apneic patient, we believe the delay of 62 minutes between first medical contact and surgical relief of tamponade might have been significantly reduced by a more focused and surgically aggressive approach. The discussion of hypercarbia's relationship to pericardial pressure based on research in dogs is interesting but, in our view, is a distraction from the practical considerations of managing the patient in extremis with penetrating truncal trauma.
To the Editor, Dr Barthélémy and colleagues' interesting case report demonstrates the importance of the identification of pericardial tamponade, the utility of ultrasound, and the possibility of excellent outcome in patients with tamponade due to a right ventricular stab wound who receive timely surgical intervention [1]. The European model of physician-based prehospital critical care remains under skeptical scrutiny in other parts of the world, and we wish to highlight that a very different and more definitive approach to pericardial tamponade due to penetrating injury would be pursued in some other physician-based systems. The authors note that they did not perform pericardiocentesis because of a lack of experience of the technique and the belief that it may be time-consuming, while also conceding that it may be futile without surgical control of the underlying cardiac wound. Impressive survival rates from prehospital clamshell thoracotomy with cardiac wound control are well documented [2], which has become established practice in a number of physician-staffed prehospital services [3,4]. We would
Cliff Reid BM Karel Habig MB BS Greater Sydney Area Helicopter Emergency Medical Service Ambulance Service of New South Wales Sydney, Australia doi:10.1016/j.ajem.2009.12.021
References [1] Barthélémy R, Bounes V, Minville V, Houze-Cerfon C, Ducasse J. Prehospital mechanical ventilation of a critical cardiac tamponade. Am J Emerg Med 2009;27:1020.e1-e3. [2] Coats TJ, Keogh S, Clark H, et al. Prehospital resuscitative thoracotomy for cardiac arrest after penetrating trauma: rationale and case series. J Trauma 2001;50(4):670-3. [3] Deakin CD. From agonal to output: an ECG history of a successful prehospital thoracotomy. Resuscitation 2007;75(3):525-9. [4] Corral E, Silva J, Suárez RM, Nuñez J, Cuesta C. A successful emergency thoracotomy performed in the field. Resuscitation 2007;75 (3):530-3. [5] Wise D, Davies G, Lockey D, Coats T, Hyde J, Goode P. Thoracotomy: how to do it. Emerg Med J 2005;22(1):22-4.