Personalised dosing of vancomycin: A prospective and retrospective comparative quasi-experimental study.

AIMS: The 2019 update to the US consensus guideline for vancomycin therapeutic monitoring advocates using Bayesian-guided personalised dosing to maximise efficacy and minimise toxicity of vancomycin. We conducted an observational cohort study of the implementation of bed-side Bayesian-guided vancomycin dosing in vascular surgery patients. METHODS: Over a 9-month prospective study period, vascular surgery patients were dosed vancomycin using Bayesian-guided dosing decision tool (DoseMeRx) and compared retrospectively with a control group admitted to the same ward in the 14 months prior to the study and dosed using a standard algorithmic approach. Primary endpoints were proportion of patients achieving mean area under the curve in 24 hours (AUC24 ) in the acceptable range 350-450 mg/L• h and percentage time in acceptable range (%TTR). Secondary endpoints focused on clinical outcomes including incidence of acute kidney injury. RESULTS: A significantly higher proportion of DoseMeRx patients achieved mean AUC24 values in the acceptable range compared to the control group; 71/104 (68.3%) vs 58/139 (41.7%), P < .005. The median %TTR was also greater in DoseMeRx patients compared to the control group (57.1 vs 30.0%, P < .00001). Patients in the DoseMeRx group missed an average of 0.23 doses per course compared to 1.04 doses in the control group (P < .00001). No difference was observed in secondary (clinical) outcomes between the 2 groups. CONCLUSION: Bedside Bayesian-guided personalised dosing of vancomycin increases the proportion of patients achieving target AUC24 and the %TTR.

A Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio® ) in cardiac surgery: the REVAKI-1 study.

AIMS: Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. There is no effective prevention or treatment. Sildenafil citrate (Revatio® , Pfizer Inc.), a phosphodiesterase type 5 inhibitor, prevents post cardiac surgery AKI in pre-clinical studies, however its use is contraindicated in patients with symptomatic cardiovascular disease. The aim of this study is to assess the safety and pharmacokinetics of intravenous sildenafil in cardiac surgery patients. METHODS: We conducted an open label, dose escalation study with six patients per dose level. The six doses were 2.5 mg, 5 mg or 10 mg as a bolus, either alone or followed by an additional 2 h infusion of 2.5 mg sildenafil. RESULTS: Thirty-six patients entered the trial, of which 33 completed it. The mean age was 69.9 years. One patient died during surgery, two others were removed from the trial before dosing (all at dose level 5 mg + 2.5 mg). The pharmacokinetic profile of sildenafil was similar to previously published studies. For a dose of 10 mg administered as a bolus followed by 2.5 mg administered over 2 h the results were AUC∞ 537 ng h ml-1 , Cmax 189.4 ng ml-1 and t1/2 10.5 h. The drug was well tolerated with no serious adverse events related to drug administration. Higher sildenafil doses stabilized post-surgery nitric oxide bioavailability. CONCLUSIONS: Pharmacokinetics of sildenafil during cardiopulmonary bypass were comparable to those of other patient groups. The drug was well tolerated at therapeutic plasma levels. These results support the further evaluation of sildenafil for the prevention of AKI in cardiac surgery.

Analgesic techniques following thoracic surgery: a survey of United Kingdom practice.

BACKGROUND AND OBJECTIVE: The authors present a national survey determining the current practice of postoperative analgesia after major thoracic surgery in the United Kingdom. METHODS: Two hundred and forty anaesthetists from 36 thoracic centres were surveyed and the response rate was 78%. RESULTS: The commonest analgesic technique after video-assisted thoracoscopic surgery is paravertebral block combined with patient-controlled analgesia with morphine. In open thoracotomy procedures, although epidural analgesia was used by a majority of the respondents, paravertebral block combined with patient-controlled analgesia with morphine is gaining popularity as an alternate technique for postoperative analgesia. CONCLUSION: The present survey demonstrates the increasing use of paravertebral block as an alternate regional anaesthetic technique to epidural analgesia after major thoracic surgery in the United Kingdom.

Fencl-Stewart analysis of acid-base changes immediately after liver transplantation.

OBJECTIVE: The Fencl-Stewart approach to acid-base physiology allows detailed, quantitative insights into acid-base disorders. We tested the hypothesis that this type of analysis would reveal complex acid-base changes in patients after liver transplantation that differed from those in a general intensive care unit population. METHODS: Data were collected retrospectively on patients on admission to the ICU after liver transplantation between 2001 and 2003 and prospectively on a convenience group of general ICU patients in 2001. RESULTS: Data were collected from 100 ICU patients and 83 liver transplant patients. Values for most clinical chemistry variables differed between the two groups, with considerable variation within the groups. All acid- base variables differed between the control and transplant groups (P < 0.005). Overall, the transplant group had metabolic acidosis (mean base excess +/-SD, -4.5 +/-3.1mmol/L) due to both a sodium chloride effect on base excess (-4.0 +/-4.1 mmol/L) and an other ion effect on base excess (-6.3 +/-4.2 mmol/L). The sodium chloride effect was mainly due to increased chloride concentration. All estimates of other anions (anion gap, corrected anion gap, strong ion gap, and the other ion effect on base excess) suggested that other anions play an important role in the acid-base status of patients after liver transplantation. These effects on base excess were partly offset by a greater metabolic alkalosis in the transplant group caused by a marked effect of decreased albumin on base excess (5.8 +/-1.5 mmol/L). CONCLUSIONS: The Fencl-Stewart approach allowed us to quantitatively assess the factors contributing to patients' acid-base status. We found complex acid-base changes in patients immediately after liver transplantation.