By Paul Mazurek
The scenario
A transport team receives a flight request to a rural hospital 35 NM away. Initial dispatch information is that you are going for an 18-year-old male with altered mental status and seizure activity. Additional information is not available at the time of initial activation as the patient had just arrived in the emergency department (ED) and the referring physician is preparing to intubate the patient.
Upon arrival of the air medical crew the story becomes more apparent. The patient was transported by his brother to the local ED after it was learned that he had ingested what was believed to be “half of a bottle” of full strength aspirin. Time of ingestion was unknown, but the young man was reported truant from school earlier that morning and was taken in by his brother after finding him on the couch unresponsive that evening.
Clinical assessment of the patient reveals an intubated, obtunded, 90 kg 18-year-old male. His pupils are 2 mm in diameter with sluggish reaction. Lung sounds reveal bibasilar rales and he is tachypneic with increased depth of respiration. He has strong central and peripheral pulses and rectal temperature is 40 degrees Celsius. In addition to the medications received during intubation (etomidate and succinylcholine), he has received a total of 26 mg of lorazepam (ativan) since arrival to the ED for refractory seizure activity and is currently receiving a midazolam (versed) infusion at 7 mg/hr.
Pertinent laboratory studies include a serum potassium level of 4.1 mEq/L, a serum salicylate level of 85.5 mg/dl, a urine pH of 6.1 and a serum creatinine of 2.1 mg/dl. An arterial blood gas drawn after intubation includes a pH of 7.21, a PaO2 of 302 mmHg, a PaCO2 0f 61 mmHg, a bicarbonate level of 20.5 and an arterial oxygen saturation of 99.8 percent. In response to this blood gas, the patient received 250 mEq of sodium bicarbonate and is currently on an infusion of 300 ml per hour. Additional intervention included 3500 ml of intravenous crystalloid and a weight appropriate dose of activated charcoal following consultation with the local poison control center.
Timing is sometimes everything
For all intents and purposes, the transport of this patient was fairly uneventful. The patient was placed on minimal ventilator settings to allow his own work of breathing to help regulate acid-base balance. He received 1.5 liters of crystalloid intravscularly during the 15-minute flight. His mean arterial pressure remained between 89 and 94 mmHg with a heart rate between 152 to 168 beats per minute. His oxygen saturation stayed between 98 and 100 percent on 0.5 fiO2 and his end-tidal CO2 remained between 52 and 55 mmHg.
Where this case becomes interesting is what happened 15 minutes after delivery to the receiving institution. Within five minutes, the patient went from warm and hyperdynamic to pale and diaphoretic. Heart rate dropped from extreme tachycardia to bradycardia, and the QRS complexes dramatically changed morphology and widened from 0.10 msec to 0.28 msec. Mean arterial pressure dropped to 50 mmHg.
Five minutes later, the patient suffered a brady-asystolic cardiac arrest and was pronounced dead twenty minutes after that.
Questions to Ponder
After the crew did their initial follow-up with the referral center and learned the patient’s final disposition, one question came to mind: what happened? Should the patient have been paralyzed and more controlled ventilatory strategies been initiated? Should the heart rate have been better controlled? Was there an additional diagnosis that was perhaps overlooked? What was missed?
The Reality of the Situation
Aspirin (acetylsalicylic acid) is one of the oldest medications in current use. It is found in a wide variety of preparations including pain relief, cold and cough remedies and topical ointments. Fatal aspirin intoxication typically occurs with the ingestion of 10 to 30 grams (one full strength aspirin is 325 mg)1. Normal aspirin levels are in the range of 10-30 mg/dl. Intoxication typically occurs when aspirin levels reach 40-50 mg/dl. Levels greater than 90 mg/dl are associated with increased morbidity and mortality2.
Primary metabolic derangements of toxicity include a mixture of respiratory alkalosis secondary to effects on the respiratory center in the brain and a metabolic acidosis; typically from an accumulation of hydrogen ions, which can inhibit ATP production and shift cellular respiration from aerobic to anaerobic2.
Acetylsalicylic acid is rapidly converted in to salicylic acid in the body. Its ability to cross cellular barriers is determined by whether or not it is in a charged or uncharged form. Uncharged molecules easily cross cellular barriers in the brain and renal tubules. Acidosis increases the plasma concentration of uncharged molecules and causes typical clinical manifestations seen in overdose1.
Central nervous system (CNS) manifestations range from tinnitus to coma, lethargy and seizures. Typical gastrointestinal (GI) symptoms include abdominal pain, nausea and vomiting. Cardiopulmonary symptoms in acute toxicity include tachypnea, tachycardia, hypotension, noncardiogenic pulmonary edema, acute lung injury and cardiovascular collapse.
Definitive treatment of acute and profound toxicity is fairly simple: hemodialysis. Management and transport priorities are supportive until the patient is in a place where they can receive this therapy. Such support includes GI decontamination with activated charcoal, fluid resuscitation for hemodynamic stability and urine alkalinization with sodium bicarbonate. The latter therapy will increase the concentration of charged salicylic acid, which tends to remain in the plasma and not cross cellular barriers.
Much of the literature discourages tracheal intubation unless absolutely necessary for airway protection or respiratory failure3,4. Aspirin acts on the respiratory center in the brain to increase the respiratory rate and thus significantly increases minute ventilation. This naturally creates an alkalotic environment to “contain” charged salicylate molecules in the blood. Inducing apnea for intubation or controlled mechanical ventilation can increase the risk for respiratory acidosis, further exacerbating the manifestations of toxicity.
Conclusion
Whenever a patient that we treat and transport dies, whether in our care at the time or not, we question what could have been done differently. This instance is no different. This particular patient needed immediate ICU and renal replacement therapy. He entered the healthcare system approximately eight hours too late and despite correct supportive treatment, never made it to definitive therapy.
References
1. Traub SJ. Aspirin Poisoning in Adults. Up to Date (v. 18.1). January 2010. Accessed 21 April 2010.
2. Adams JG et. al. Emergency Medicine. Philadelphia. Saunders-Elsevier. 2008. pp. 1519-1521.
3. Stolbach AI, Hoffman RS and Nelson LS. Mechanical Ventilation was Associated with Acidemia in a Case Series of Salicylate-Poisoned Patients. Academic Emergency Medicine (15). 2008. pg. 866.
4. Greenberg MI, Hendrickson RG and Hofman M. Deleterious Effects of Endotracheal Intubation in Salicylate Poisoning. Annals of Emergency Medicine (41). 2003. pg. 583.
