Multiparametric evaluation of sedation in the ICU

Introduction

A problem for patients submitted to extended sedation is evidence of a liver dysfunction. We wanted to verify whether this dysfunction is either correlated with the splanchnic hypoperfusion or with the extended administration of drugs.

Methods

During March–September 2007, four patients with pure cranial trauma (age 34–50 years) were treated with midazolam, propofol, sodium thiopental and fentatienil. Parameters evaluated: burst suppression ratio (BSR) with electroencephalography (Aespect; GE Health Care), functional capillary density (FCD) and mean velocity with Microscan and MAS (MicroVision Medical, Amsterdam, The Netherlands), plasma disappearance ratio (PDR) with Pulsion LIMON (SEDA; Milano), intramucosal pH and regional PCO₂ with Tonocap (GE Health Care), electrocardiography, mean arterial pressure and hematochemical examinations (transaminases, γ-glutamyl transpeptidase (GGT), serum bilirubin, serum amylases, serum lactates and drugs dosages). Exclusion criteria: hepatopathy at admission, age <18 years and >60 years, BMI > 30, clinical factors favouring splanchnic hypoperfusion. All the parameters are analysed at t0 (admission to the ICU) and then every 48 hours during the sedation (t1, t2, t3) and at its end (t4, t5) through the Friedman test (P < 0.05) and the Spearman test (P < 0.05 and R > 0.6).

Results

Increase of transaminases at the end of sedation in three of the four patients. Earlier increase of GGT in all patients. Serum bilirubin always in range. Increase of serum amylases in three of the four patients is correlated to propofol dosage. PDR always >16%/ml (cutoff of hepatic hypoperfusion). BSR always >0% during t1, t2, t3. FCD always steady and mean velocities always high. Hepatic cytonecrosis indexes, GGT, serum amylases are well correlated to splanchnic perfusion indexes (serum lactates, FCD and regional PCO₂) so their increase apparently is not due to splanchnic hypoperfusion. Patient 1 (propofol, fentatienil early replaced with sodium thiopental, midazolam), increase of transaminases when midazolam was stopped. Because of the beginning of an epileptic status, the patient was eliminated from the study. Patient 2 (propofol, midazolam, fentatienil), increase of transaminases associated with the paradoxical increase of splanchnic perfusion. Patient 3 (propofol, midazolam, fentatienil), increase of transaminases and serum amylases is not associated with the splanchnic hypoperfusion. Serum amylases increase according to the increase of propofol dosage. Patient 4 (propofol, fentatienil), late increase of transaminases, serum amylases and GGT is associated with the propofol dosage.

Conclusion

Drugs used for the analgosedation seem responsible for the increase of transaminases but not for the decrease of splanchnic perfusion. This study has to be confirmed by other studies recruiting more patients and with more precise exclusion criteria.