Propofol Infusion Syndrome—A Fatal Case at a Low Infusion Rate

To the Editor:

We report the case of a 24-year-old male athlete who sustained a spinal injury, while competing in a Swiss wrestling contest. His third cervical vertebra was fractured, producing incomplete sensory and motor paraplegia. Upon admission to a regional hospital, the patient was treated with IV large-dose methylprednisolone (¹). He unfortunately suffered from massive aspiration during initial magnetic resonance imaging, followed by acute respiratory distress syndrome (ARDS) and systemic inflammatory reaction syndrome (SIRS). The patient's trachea was intubated and his lungs were mechanically ventilated. He was sedated with propofol at a maximum infusion rate of 2.6 mg·kg⁻¹· h⁻¹. He required moderate adrenergic support. Cardiac troponin I (Trop I) and creatine kinase (CK) were increased 14 and 52 h after initiation of propofol sedation. (Fig. 1) The patient developed acute renal failure and was transferred to our hospital, a tertiary referral center, for further therapy. Before dialysis could be started, he suffered from pulseless bradycardia because of hyperkalemia, followed by massive cerebral edema. Further therapy was withheld, and the patient died.

Figure 1.: Course of CK and Trop I levels and timing of medication. Immediately upon admission to the primary care hospital, steroids were given as an initial bolus infusion of 30 mg/kg followed by an infusion of 5.4 mg· kg⁻¹ · h⁻¹ for 23 h (¹). Four hours after admission, sedation with propofol at a maximum infusion rate of 2.6 mg·kg⁻¹ · h⁻¹ (mean 1.9 mg· kg⁻¹ · h⁻¹) was started after tracheal intubation because of aspiration. The patient developed ARDS with an increasing need of catecholamine support 24 h after admission (dopamine: maximum 3.5 μg/min, norepinephrine: maximum 12 μg/min). Elevated CK was measured initially after 52 h (830 U/L) and increased Trop I after 14 h (3.56 ng/mL), after initializing sedation. Sedation with propofol was stopped upon admission to the tertiary referral hospital. Maximum level of CK and Trop I was 486,900 U/L and 6.3 ng/mL, respectively, on Day 6. The bars denote the timing of medication.

Propofol infusion syndrome is defined by severe metabolic acidosis, rhabdomyolysis, renal failure, and cardiac failure in association with a prolonged propofol infusion, critical illness, and concurrent administration of catecholamines and steroids (²). Evidence for dose-dependent association between propofol use and propofol infusion syndrome (³) has led to guidelines recommending maximum propofol infusion rates of 4.8 mg· kg⁻¹·h⁻¹ (⁴) for long-term sedation in intensive care unit patients. Recent case reports describe propofol infusion syndrome after short-term (3–6 h) infusions, if infusion rates are high (^5–7). Our patient presented with the features of propofol infusion syndrome. We have no other explanation for his rhabdomyolysis and cardiac failure. He received markedly less propofol than the maximum doses currently considered safe. To our knowledge, this is the first case of suspected propofol infusion syndrome in a patient receiving such low propofol infusion rates. We suggest considering alternative sedation regimes when risk factors for propofol infusion syndrome are present: ARDS, SIRS, and treatment with large-dose steroids or catecholamines.

Tobias M. Merz, MD

Bruno Regli, MD

Hans-Ulrich Rothen, MD, PhD

Clinic of Intensive Care Medicine

University Hospital Bern

Bern, Switzerland

[email protected]

Peter Felleiter, MD

Intensive Care Unit

Swiss Paraplegic Centre Nottwil

Nottwil, Switzerland