Pharmacokinetics of colistin in critically ill patients with multidrug-resistant Gram-negative bacilli infection.

PURPOSE: Colistin, which had not been used widely because of nephrotoxicity and neurotoxicity, has gained clinical importance in recent times due to the resurgence of multidrug-resistant Gram-negative bacilli. Very few studies, especially pharmacokinetic studies, have been performed with intravenous colistimethate sodium, and none in India. The aim of our study was to study the single-dose and steady-state pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative bacilli infections. METHOD: This was a prospective open-label pharmacokinetic study done in an intensive care unit in a tertiary care hospital on 15 critically ill patients with proven multidrug-resistant Gram-negative bacilli infection. Colistimethate sodium was injected as intermittent intravenous infusions in accordance with the recommendations on the package insert. For patients weighing ≥ 60 kg with a normal renal function or with a creatinine clearance (CL(CR)) of between 20 and 50 ml/min, the drug was administered at 2 million international units (MIU) every 8 h; for those with a CL(CR) of 10-20 ml/min, the dose was 2 MIU every 12 h. Those patients who weighed <60 kg were administered 50,000 IU/kg/day in three divided doses at 8-h intervals. Both single-dose and steady-state pharmacokinetics of colistin were determined and correlated with clinical outcomes. RESULTS: A wide inter-individual variation was observed in pharmacokinetic parameters. The median (range) of the maximum plasma drug concentration/minimum inhibitory concentration (C(max)/MIC) ratio for Acinetobacter spp. was 13.4 (1.3-40.3) following the administration of a single dose of colistimethate sodium and 26.3 (0.9-64.9) at steady-state. For Pseudomonas spp., these values were 3.18 (1.6-23.1) following the single dose and 3.82 (2.3-10.9) at steady-state. For those patients whose cultures grew Acinetobacter spp., an optimum value of the C(max)/MIC ratio of >8 was achieved in seven of nine patients after the single dose and in seven of eight patients at steady-state. For those patients whose cultures grew Pseudomonas spp, only one patient after the single dose and one patient at steady-state achieved a C(max)/MIC ratio of >8. A significant association was noted between dose and survival, and a trend was observed with patients weighing ≤ 60 kg (who received 50,000 IU/kg/day instead of 6 MIU/day for those >60 kg) having an increased mortality. CONCLUSION: The pharmacokinetic parameters of colistin were comparable to those reported in previous studies in critically ill patients. However, the recommended dose may be inadequate to maintain the C(max)/MIC ratio to an optimal level-at least in patients infected with Pseudomonas spp. The dose recommendation should be based only on creatinine clearance and not body weight.

Evaluation of Intubating Conditions with Varying Doses of Propofol without Muscle Relaxants.

BACKGROUND: Since 1988 anaesthesiologist have proved that induction dose of propofol is sufficient to intubate patient without muscle relaxants. Propofol is unique in having property to suppress airway reflexes better than any other agent. Therefore study was undertaken to evaluate clinically acceptable intubating conditions with different doses of propofol without muscle relaxants. PATIENTS AND METHODS: 90 ASA grade I and II patients posted for elective surgery requiring general anesthesia divided randomly into group I (propofol 2 mg kg(-1)); group II (2.5 mg kg(-1)); groupIII (3mg kg(-1)). Premedication with inj.Glycopyrollate, inj.Ranitidine, Inj.Ondensetron; inj.Midazolam and inj.fentanyl was done. After waiting for 5 minutes, induction dose of propofol was given followed by inj.lignocaine 90 seconds prior to intubation. Intubating conditions were assessed and hemodynamic changes were recorded at various levels. RESULTS: Ideal intubating conditions were obtained in 96.7%of patients in group II (2.5 mg kg(-1) propofol) and 100% in group III (3 mg kg(-1) propofol). We found that clinically acceptable intubating conditions can be achieved with 2.5 mg kg(-1) and 3 mg kg(-1) propofol without significant hemodynamic changes and 100% success can be obtained with 3 mg kg(-1) of propofol CONCLUSION: Ideal intubating conditions without muscle relaxants can be achieved with propofol 3 mg kg(-1) with fentanyl 2 µg kg(-1) and lignocaine 1.5 mg kg(-1) without significant hemodynamic changes.