Propofol is an intravenous sedative hypnotic agent which rapidly and reliably causes loss of consciousness. It is also associated with a quick and 'smooth' recovery, which distinguishes it from many of the more traditional anaesthetic regimens. Like other intravenous agents, propofol is both a cardiovascular and a respiratory depressant; however, the risk of these effects can be lessened by appropriate dosage adjustment or patient management. Anaphylaxis with propofol is rare. Propofol anaesthesia in day case surgery is consistently associated with a quicker early recovery than other intravenous agents and the more traditional anaesthetic regimens. Savings in time to discharge were more variable compared with these regimens, although propofol was commonly associated with less post-operative nausea and vomiting in this period. In the future, the relative benefits of propofol compared with the newer volatile agents (desflurane and sevoflurane) and propofol/volatile agent combinations need to be examined in this clinical setting. There is now clinical experience with propofol in major surgical procedures including cardiac and neurosurgery. Propofol has also been investigated as a sedative accompanying regional or local anaesthesia for diagnostic and therapeutic procedures, and in other clinical settings (ophthalmic surgery, cardioversion and electroconvulsive therapy). The unique antiemetic, antiepileptic and antipruritic effects of propofol may further broaden its appeal. As a result of its favourable recovery profile, propofol holds a central place in day case surgery anaesthesia. Accumulating clinical experience in cardiac and neurosurgery suggests that the full potential of propofol has yet to be realised.

Propofol. An update of its use in anaesthesia and conscious sedation.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/lt.20108

The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: A systematic review and meta-analysis

Nonabsorbable antibiotics for selective bowel decontamination (SBD) sometimes are administered to liver transplant patients to prevent postoperative infections, but the efficacy of SBD is not known. Accordingly, we prospectively studied 69 patients randomly assigned to receive conventional prophylaxis with systemic antibiotics (control patients) or conventional prophylaxis plus oral nonabsorbable antibiotics for SBD (SBD patients). Overall rates of bacterial and/or yeast infections were nearly equal among control patients (42%) and SBD patients (39%). However, the infection rate at SBD key sites (abdomen, bloodstream, surgical wound, and lungs) was lower among patients who received the SBD regimen > or = 3 days before transplantation (23%) than among control patients (36%). Administration of the SBD regimen was complicated by gastrointestinal intolerance and noncompliance but not by increased stool colonization with antibiotic-resistant gram-negative bacilli. Practical problems associated with administering an SBD regimen to patients awaiting cadaver liver transplants limit the regimen's usefulness, but we found a trend toward reduced key site infection when the regimen was given > or = 3 days before transplantation.

/pdf/randomized-controlled-trial-of-selective-bowel-4mceinx8rc.pdf

Randomized Controlled Trial of Selective Bowel Decontamination for Prevention of Infections Following Liver Transplantation

Kidney transplantation is now recognized as the treatment of choice for patients with chronic renal failure. Despite the extension of indications to patients suffering severe hypertension, ischemic heart disease, and chronic heart failure, the worldwide results are superb. However, perioperative cardiac complications occur in 6% to 10% of transplanted patients. Aggressive intraoperative volume expansion is still recommended to maximize graft functional recovery (up to 30 mL/kg/h, central venous pressure [CVP] > 15 mm Hg), but patients with preexistent cardiac disease or poor myocardial function are exposed to the risk of fluid overload, acute respiratory failure, and prolonged ventilation. Among the last 90 cases performed at our institution, good functional recovery of the graft was present in 94% of the patients within 2 weeks, despite a much more conservative intraoperative hydration policy (crystalloids 2400 +/- 1000 mL, 15 mL/kg/h, CVP 7-9 mm Hg). Graft failure which occurred in 5 patients was significantly correlated only with donor age, while perioperative cardiovascular complications had been present in 9 cases (10%) who were coronary artery disease patients (55%). Age above 50 years was the only significant risk factor. Supranormal volume loading is probably not always warranted in kidney transplantation.

Perioperative fluid management in kidney transplantation : Is volume overload still mandatory for graft function?

To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P<-0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/1 in 47 of 49 patients from group A, while they plateaued above 4 mmol/1 in all patients from group B. Group A patients had lower alanine aminotransferase levels (P<-0.001), higher prothrombin activity, (P<-0.01), and greater bile flow (P<-0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.

Lactate blood levels in the perioperative period of orthotopic liver transplantation.

Study objective To define the pharmacokinetic profile of the induction dose of propofol in chronic renal failure patients. Design and setting Determination of propofol blood concentrations after the bolus dose of 2 mg.kg-1 bw injected in 30 seconds in a peripheral vein in a group of chronic renal failure (CRF) patients and in a group of normal patients (controls). Patients 10 CRF patients (7 males, 3 females, mean age 47 +/- 8 years old, mean body weight 66 +/- 8 kg) candidates to cadaveric renal transplantation and free from major hepatic diseases (study group); 8 ASA I patients (5 males, 3 females), without major cardiorespiratory, hepatic, renal, hematologic or metabolic diseases undergoing minor elective surgical procedures lasting from 50 to 90 minutes (control group). Measurements a) propofol blood concentrations by means of HPLC; b) derived pharmacokinetic parameters (calculated by means of Siphar, version 4.0, Societe de informatique medicale, Simed, Paris, 1991); c) cardiovascular parameters (heart rate, central venous pressure, invasive arterial pressure). Main results The decay of propofol whole blood concentrations, distribution, redistribution and elimination half lives were similar in CRF and in control patients. On the contrary, significantly different in CRF patients were propofol blood concentrations from two to ten minutes following the induction dose (lower), the area under concentration- time curve (AUC) (smaller), the mean resident time (longer), the total body clearance (greater), the volumes of distribution at steady state and during the elimination phase (larger). The larger volumes of distribution are closely correlated with the significantly lower albumin concentrations in the uremic patients. An accelerated hepatic biotransformation is one of the possible explanations for the greater total body clearance of propofol in the uraemic patients: in fact an increased glucuronyltrasferase activity and glucuronoconjugation induced by phenols has been demonstrated in uraemia. On the other hand, large volumes of distribution are often associated with elevated total body clearance. The only significant change in the cardiovascular profile was a reduction of 17 +/- 8% of the systolic blood pressure one minute after the administration of the induction dose of propofol, whereas heart rate, arterial and central venous pressures were rather stable after intubation and at skin incision: proper vascular filling before the induction of anaesthesia has probably played a crucial role in maintaining hemodynamic stability. Conclusions From the data gathered in this study, propofol can be considered a suitable anaesthetic agent for the induction of general anaesthesia in uraemic patients. In our opinion these data could constitute a basis for future protocols of total intravenous anaesthesia with propofol in uremic patients.

Pharmacokinetic profile of the induction dose of propofol in chronic renal failure patients undergoing renal transplantation.

Early severe infections after orthotopic liver transplantation.

Atrial natriuretic factor (ANF) is a 28 amino acid peptide secreted by the atrial cardiocytes. Clearance is via the lung (50%) and the liver (25%). The main stimulus to ANF secretion is atrial distension but vasoconstrictors, sympathetic stimulation, catecolamines and tachycardia are able to enhance its circulating blood levels. ANF blood concentrations were measured during orthotopic liver transplantation in six postnecrotic cirrhotic patients. Significant increases in ANF blood levels occurred at the end of the anhepatic phase (P≤ 0.02 vs baseline) associated with low cardiac filling pressures (P≤ 0.02 vs baseline) and increased systemic vascular resistances (P≤ 0.02 vs preanhepatic phase). Aldosterone blood levels showed a similar behaviour, increasing significantly (P≥ 0.001 vs baseline) at the end of the anhepatic phase. ANF fell after reperfusion of the graft and returned towards baseline values at the end of the procedure. Since most of the total body clearance of ANF is performed by the lungs, its sharp increase at the end of the anhepatic phase could be considered a counterregulatory response to vasoconstricting stimulation and to fluid-paring mechanisms in the presence of relative hypovolaemia. Its decrease after reperfusion could be related to volume normalization and partly to the enhanced clearance performed by the newly grafted liver.

Changes in circulating levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation in humans

The initial disposition of propofol was reported to change when the administration was preceded by fentanyl. The pharmacokinetic profile of the induction dose of propofol (2 mg kg-1 body weight) was studied in 20 ASA I patients randomly allocated to receive fentanyl 1.5 microgram kg-1 (n = 12) or not (n = 8). Anaesthesia was maintained with isoflurane in N2O/O2. Venous blood drawn from the contralateral arm was used to determine whole blood propofol concentrations. The mean propofol blood concentrations were comparable in the two groups and were best fitted by a three exponential equation in all the patients, conforming to a three-compartment open mammillary model. Distributions (T1/2 alpha) redistribution (T1/2(7)) and elimination (T1/2 beta half-lives were comparable in the groups, without significant differences in the total body clearance in the area under the time-concentration curve (zero-infinity) in the volume of distribution at steady-state, in the volume of distribution during the elimination phase or in the mean resident time. Our data support the conclusion that pretreatment with fentanyl does not affect the pharmacokinetic profile of the induction dose of propofol in ASA I patients.

Fentanyl pre-treatment does not affect the pharmacokinetic profile of an induction dose of propofol in adults.

Endotoxemia following liver transplantation in humans.

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