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Dantrolene for severe rhabdomyolysis in Staphylococcus aureus toxic shock syndrome

Ginz, Hans F.; Levano, Soledad; Girard, Thierry; Urwyler, Albert; Hamel, Christian

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European Journal of Anaesthesiology: March 2012 - Volume 29 - Issue 3 - p 161-162
doi: 10.1097/EJA.0b013e32834c7c9d

Editor,

Thanks to antibiotics, mortality of Staphylococcus aureus bacteraemia has decreased from 80 to 28%.1 When S. aureus produces enterotoxins or toxic shock syndrome toxins, mortality increases to 56%.2 We report on a patient with toxic shock syndrome who was successfully treated with antibiotics and dantrolene. Written consent regarding the information in this article was obtained from the patient.

A 61-year-old male patient, BMI 42 kg m−2, who underwent cholecystectomy 18 years earlier, was scheduled for surgery of a cutaneous fistula. Anaesthesia was performed with thiopentone 3 mg kg−1, succinylcholine 1 mg kg−1, cisatracurium 0.1 mg kg−1 and 1.5 vol% isoflurane. Three days after index operation, the patient complained of back pain. His cardiocirculatory status deteriorated drastically, and so his trachea was intubated and lungs were ventilated with 100% oxygen. Blood gas analysis was pO2 80 Torr (mmHg), pH 7.24, HCO3 14.8 mmol l−1, base excess −10.8 mmol l−1 and lactate 7.71 mmol l−1. The patient required fluid resuscitation and catecholamines. He had a 40.1°C fever and the β-lactamase antibiotic, meropenem, was administered. Wound infection, pneumonia and endocarditis were excluded. Procalcitonin was 109.4 ng ml−1 (normal range 0.05–0.5), C-reactive protein 28.9 mg dl−1 (<0.82) and leukocytes 17 000 nl−1 (4300–10 000). The patient developed rhabdomyolysis [creatine kinase 49 302 U l−1 (<171), myoglobin 92 663 μg l−1 (<96.5)]. In order to stop skeletal muscle hypermetabolism, 12 × 20 mg vials of dantrolene (1.8 mg kg−1) were administered. The patient underwent surgical revision without any abnormal findings. He required haemodiafiltration for 2 weeks.

From the wound and blood samples, S. aureus-producing toxic shock syndrome toxins A, B and D were isolated (negative enterotoxin C, toxic shock syndrome superantigen, Panton–Valentine leukocidin). Nasal and liquor cultures were not colonised. Rifampicin was administered and the patient slowly recovered. He suffered from a severe critical illness myopathy and was discharged to a rehabilitation unit after 6 weeks. After 1 year of hospitalisation, the patient was discharged to a home, as he still required a wheelchair because of skeletal muscle weakness.

Dantrolene was administered to treat the patient's continuous fever, due to skeletal muscle hypermetabolism. Dantrolene binds to ryanodine-1 receptor and inhibits calcium release from the sarcoplasmic reticulum and, hence, stops hypermetabolism.3 Creatine kinase value decreased to 50% of maximum after 1 day. Although diagnosis of malignant hyperthermia is unlikely 3 days after inhalational anaesthesia, we sequenced the complete ryanodine-1 receptor coding sequence. The genomic sequences had only synonymous single nucleotide polymorphisms (Table 1) and we could not identify any mutation causative for malignant hyperthermia (http://www.emhg.org/genetics/mutations-in-ryr1/). However, as an in-vitro contracture test was not performed, malignant hyperthermia cannot be definitively excluded. Alternatively, hypermetabolism could have originated from S. aureus sepsis. It is also worth mentioning that we lost another patient also suffering from rhabdomyolysis (myoglobin 90 543 μg l−1) caused by S. aureus-producing toxic shock syndrome toxins A and B. Although this patient underwent the same therapy, dantrolene was not available in this case.

Table 1
Table 1:
Single nucleotide polymorphisms in the coding region of the ryanodine-1 receptor in a patient with severe rhabdomyolysis

About 20% of the (healthy) human population are nasal carriers of S. aureus.4 Bode et al.4 described a reduction in the number of surgical site S. aureus infections by early screening and decolonising of nasal carriers of S. aureus. Perl et al.5 reported no evidence that mupirocin treatment reduced the incidence of infection. Nevertheless, the nosocomial infection rate was decreased. We suggest that large and long-existing fistulas may be colonised by S. aureus which could be harmful even for healthy patients. Thus, topical mupirocin treatment before surgery may be of consideration.

In conclusion, in toxic shock syndrome with skeletal muscle hypermetabolism, dantrolene treatment may be taken into account early on, if specific antibiotic therapy alone is not successful. For the future, a more concentrated dantrolene suspension may be desirable to save time in such cases of illness.6

Acknowledgements

No financial support was received for this study.

None of the authors has any conflict of interest.

Work was performed at the Division of Operative Critical Care, Department of Anaesthesia, County Hospital, Lorrach, Germany.

References

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© 2012 European Society of Anaesthesiology