Sickle cell disease: high levels of norpethidine increased the risk of fits.

Clinical bottom line (level 4)

  1. Patients with sickle cell disease who had levels of norpethidine >1.0 µ g/l, were at an increased risk of fitting.
Pryle et al: British Medical Journal 1992; 304: 1478-1479
Expires December 2003

The study

Case-control study with objective outcomes, not adjusted for confounding factors, not validated in an independent set of patients.

Setting: university hospital, UK

16 patients (aged ?, ?% male) sickle cell disease
Cases: 2 patients (% male, mean age ): sickle cell disease with grand mal seizures while receiving high dose pethidine
Controls: 14 patients (% male, mean age ): sickle cell disease

Factors studied:
  • seizures


    • Factors summarised:
  • norpethidine >1.0 µ g/l


    • Outcomes studied:
  • convulsion within a few hours of sampling

    • The evidence

    Patient expected event rate for convulsion within a few hours of sampling: 19%
    risk factor for
    convulsion within a few hours of sampling     		unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    norpethidine >1.0 µ g/l inf
    (5.5 to inf)     		1
    (1 to 200)

    • Of the patients that fitted, two took oral pethidine at home and another had renal impairment. All had a pethidine dose of >25 mg/kg/day.
    • Gas chromatography was used to measure pethidine and norpethidine.

    Citation

    1. Pryle BJ, Grech H, Stoddart PA, et al: Toxicity of norpethidine in sickle cell crisis. British Medical Journal 1992; 304: 1478-1479
    Contributor: Nick Shenker and Clare Wotton, May 2000
    Reviewer:

    Clinical Question.
    Patient sickle cell disease
    Intervention or Exposure pethidine
    Outcome high norpethidine concentration