CASE HISTORY – January 2016

Dosing of medicines in a superobese patient: a clinical case

Authors: Jana Lass, Kadri Tamme, Alar Irs

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A 54 year old man (body mass index 79 kg/m2) was admitted to Tartu University Hospital with bilateral pneumonia and acute respiratory failure. He was intubated and kept on mechanical ventilation; antibacterial treatment and thrombo-prophylaxis with low molecular weight heparin were provided. Haemophilus infuenza and Streptococcus pneumoniae were identified as the causative organisms with superinfection by Pseudomonas aeruginosa complicating the disease. Pneumonia responded to treatment with multiple antibiotics, however, there developed pulmonary embolus with obstructive shock, and acute liver and renal failure. Thrombolysis and continuous haemodiafiltration were performed. Episodes of atrial flutter compromised haemodynamic stability. Increase in inflammatory markers necessitated further antibacterial treatment. The patient recovered after 76 hospital days, of these 56 spent in an intensive care unit. Altogether 48 different medicines were administered during his hospital stay.

The case illustrates difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing while data on adequate doses of medicines are scarce. Obesity may influence the võlume of distribution, binding to plasma proteins, metabolism and elimination. Obesity related changes in the liver (steatosis and nonalcoholic steatohepatitis, NASH) and renal functions are reflected in metabolism and in the clearance of medicines. The NASH may either increase or decrease the expression of CYP enzymes; increase in blood võlume and cardiac index may enhance clearance by the liver.The eGFR and tubular secretion have been reported to increase in obesity. None of the weight estimates used to dose medicines (total body weight, actual body weight, lean body mass, ideal body weight) is universally optimal in obesity.

Limited available data for dosing medicines in obesity used in this case is discussed, with emphasis on antimicrobials and anticoagulants.