Respiratory Arrest Associated With Polymyxin B in a Lung Transplant Patient

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Respiratory Arrest Associated With Polymyxin B in a Lung Transplant Patient

Multidrug-resistant (MDR) bacterial infections are a growing crisis for critically ill patients—especially those who’ve undergone organ transplants, where weakened immune systems make them more vulnerable. For doctors, polymyxin B (PMB)—a “last-resort” antibiotic first used in the 1950s—has become a critical tool when other drugs fail. But a 2020 case report from China-Japan Friendship Hospital warns of a rare, life-threatening risk: sudden respiratory arrest linked to PMB use in lung transplant recipients.

The case centers on a 67-year-old man who received a left single lung transplant for end-stage idiopathic pulmonary fibrosis in October 2018. His post-op course was smooth initially: he left the ICU on day 3, walked without oxygen, and followed standard immunosuppressive (tacrolimus, mycophenolate mofetil, methylprednisolone) and antimicrobial prophylaxis. But on day 14, he developed a productive cough, high white blood cell count, and elevated procalcitonin—a sign of infection. A chest X-ray showed infiltrates in his left lower lobe, and bronchoscopy revealed purulent secretions. The culprit? Carbapenem-resistant Acinetobacter baumannii (CRAB), a “superbug” sensitive only to PMB (minimum inhibitory concentration [MIC] ≤0.5 mg/mL) and tigecycline (MIC = 2 mg/mL).

His doctors started IV PMB (25,000 IU/kg daily, split into two doses) plus tigecycline (100 mg every 12 hours). At the time, his serum creatinine was slightly elevated (112.9 mmol/L, above the normal 35–106 mmol/L range)—a red flag for kidney function, since PMB is cleared by the kidneys.

Two days later, he reported mild chest tightness and leg weakness. On day 3 of PMB treatment, 30 minutes into an infusion, he suffered sudden hypercapnic respiratory failure (pH 7.004, PaCO₂ 83.6 mmHg, PaO₂ 105 mmHg on 50% oxygen). Non-invasive ventilation failed, so he was intubated. He recovered quickly and was extubated within 24 hours—but 8 days later, the same crisis struck again during a PMB infusion.

Doctors ruled out all other possible causes: pulmonary embolism, pneumothorax, airway blockage, electrolyte imbalances, stroke, or epilepsy. The patient later described the episode as “being fully aware but unable to breathe”—a classic sign of neuromuscular blockade, a known (but rare) side effect of PMB. A diaphragm ultrasound showed thinning and reduced movement, confirming respiratory muscle paralysis.

Using the Naranjo Adverse Drug Reaction Probability Scale—a tool to link symptoms to medications—his score was 9, meaning a definite connection between PMB and respiratory arrest. PMB was stopped immediately. His doctors switched to sulbactam (combined with tigecycline) to treat the CRAB infection. He was extubated again, had no further breathing issues, and was discharged 1.5 months after his transplant.

Why This Matters for Patients and Doctors

PMB is invaluable for MDR infections like CRAB, which kill up to 50% of patients who get them. But this case highlights a critical gap: neuromuscular blockade is a rare but potentially fatal complication. For lung transplant patients—who already face fragile respiratory function—even a brief loss of breathing muscle control can be catastrophic.

The team behind the case identified key risk factors for their patient:

  1. Newer drug approval in China: PMB was only approved by China’s FDA in 2017, so dosing and monitoring protocols were still evolving.
  2. Lack of therapeutic drug monitoring: International guidelines (endorsed by the Infectious Diseases Society of America [IDSA] and European Society of Clinical Microbiology and Infectious Diseases [ESCMID]) recommend tracking PMB levels to avoid toxicity—but this wasn’t done initially.
  3. Mild kidney dysfunction: PMB is cleared by the kidneys, so reduced function can build up drug levels and increase neurotoxicity.
  4. Infusion time: The patient received PMB over 1 hour; longer infusions (2+ hours) may lower risk, though more research is needed for transplant patients.

Importantly, PMB-induced paralysis is reversible—nearly 70% of patients recover fully if the drug is stopped quickly. But early recognition is key: symptoms like muscle weakness, chest tightness, or difficulty breathing during infusions need urgent attention.

The Big Picture

For doctors, PMB remains a lifeline for MDR infections. But this case is a reminder to use it cautiously:

  • Monitor kidney function: Especially in patients with pre-existing renal issues.
  • Use therapeutic drug monitoring: Follow international guidelines (targeting a 24-hour area under the curve of 50–100 mg·h/L) to balance efficacy and safety.
  • Watch for early warning signs: Leg weakness, chest tightness, or shortness of breath during infusions.

This case was reported by Wen-Hui Chen, Lan Lin, and colleagues from the Department of Lung Transplantation at China-Japan Friendship Hospital (Beijing, China) and Fujian Medical University Union Hospital (Fuzhou, China). It was published in the Chinese Medical Journal in 2020 (Volume 133, Issue 11).

doi.org/10.1097/CM9.0000000000000826

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