Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomised, placebo-controlled, double-blinded clinical trial.

BACKGROUND: Ketamine is routinely used in operating theatres, emergency departments, ICUs, and even outpatient units. Despite the widespread use of ketamine, only basic aspects of its interactions with inhalation anaesthetic agents are known, and formal testing of interactions in humans is lacking. The minimum alveolar concentration (MAC) of inhalation anaesthetics is used to guide the depth of anaesthesia, and several drugs are known to influence the MAC. The aim of this study was to investigate whether intravenous application of ketamine influences the MAC of sevoflurane in humans. METHODS: Adult patients undergoing elective surgery were included in this randomised, double-blinded, placebo-controlled study. Patients were assigned to one of three groups, each of which received a bolus of placebo, 0.5 mg kg-1S-ketamine, or 1 mg kg-1S-ketamine followed by an infusion of the same amount per hour after inhalation induction with sevoflurane was performed. The response to skin incision (movement vs non-movement) was recorded. The MAC of sevoflurane was assessed using an up-and-down titration method. RESULTS: Sixty patients aged 30-65 yr were included. Each group consisted of 20 patients. The MAC of sevoflurane was higher in the placebo group (2.1 (sd 0.1) %) than in the low-dose ketamine group (0.9 (0.1)%, P<0.01) and the high-dose ketamine group (0.5 (0.1)%, P<0.01). In addition, the MAC of sevoflurane was higher in the low-dose ketamine group compared with the high-dose ketamine group (P<0.01). CONCLUSIONS: The administration of S-ketamine significantly and dose-dependently reduced the MAC of sevoflurane in humans. CLINICAL TRIAL NUMBER: EudraCT ref. no. 2012-001908-38.

Feasibility of a 'reversed' isolated forearm technique by regional antagonization of rocuronium-induced neuromuscular block: a pilot study.

BACKGROUND: The isolated forearm technique is used to monitor intraoperative awareness. However, this technique cannot be applied to patients who must be kept deeply paralysed for >1h, because the tourniquet preventing the neuromuscular blocking agent from paralysing the forearm must be deflated from time to time. To overcome this problem, we tested the feasibility of a 'reversed' isolated forearm technique. METHODS: Patients received rocuronium 0.6 mg kg(-1) i.v. to achieve muscle paralysis. A tourniquet was then inflated around one upper arm to prevent further blood supply to the forearm. Sugammadex was injected into a vein of this isolated forearm to antagonize muscle paralysis regionally. A dose titration of sugammadex to antagonize muscle paralysis in the isolated forearm was performed in 10 patients, and the effects of the selected dose were observed in 10 additional patients. RESULTS: The sugammadex dose required to antagonize muscle paralysis in the isolated forearm was 0.03 mg kg(-1) in 30 ml of 0.9% saline. Muscle paralysis was antagonized in the isolated forearm within 3.2 min in nine of 10 patients; the rest of the patients' bodies remained paralysed. Releasing the tourniquet 15 min later did not affect the train-of-four count in the isolated forearm but significantly increased the train-of-four count in the other arm by 7%. CONCLUSIONS: Regional antagonization of rocuronium-induced muscle paralysis using a sugammadex dose of 0.03 mg kg(-1) injected into an isolated forearm was feasible and did not have relevant systemic effects. CLINICAL TRIAL REGISTRATION: The trial was registered at EudraCT (ref. no. 2013-002164-53) before patient enrolment began.

Intravenous lidocaine increases the depth of anaesthesia of propofol for skin incision--a randomised controlled trial.

BACKGROUND: The anaesthetic potency of intravenous propofol is quantified by its Cp50 value, which is defined as the plasma concentration required to prevent movement response in 50% of patients to surgical stimuli. We hypothesised that, in addition to propofol anaesthesia, an intravenous bolus of lidocaine 1.5 mg/kg will decrease the Cp50 value of propofol during anaesthesia. METHODS: We enrolled 54 elective surgical patients undergoing propofol-based anaesthesia, and randomised them to either lidocaine 1.5 mg/kg, lidocaine 0.5 mg/kg or placebo (NaCl 0.9%) 3 min before skin incision. The propofol Cp50 value was then calculated using the 'up-and-down' method of Dixon and Massey. RESULTS: There was no significant reduction in propofol requirements after the administration of 0.5 mg/kg lidocaine from 8.5 µg/ml [confidence interval (CI) 6.0-11.625] to 8.25 µg/ml (CI 6.75-9.76); however, a bolus of 1.5 mg/kg lidocaine decreased the Cp50 value of propofol by 42% from 8.5 µg/ml (CI 6.0-11.625) to 4.92 µg/ml (CI 4.5-5.78) (P < 0.05). CONCLUSION: An intravenous bolus injection of 1.5 mg/kg lidocaine 2% caused a significant reduction of the propofol Cp50 value.

Levosimendan infusion improves haemodynamics in elderly heart failure patients undergoing urgent hip fracture repair.

BACKGROUND: Elderly patients with heart failure undergoing urgent major surgery suffer substantial cardiac morbidity and mortality. Levosimendan, a novel calcium sensitizer, enhances myocardial contractility while simultaneously having vasodilatory and cardioprotective properties. This could be advantageous in perioperative management of heart failure patients. METHODS: Ten consecutive patients with symptomatic heart failure and left ventricular ejection fraction <35% undergoing urgent hip fracture repair were studied. Levosimendan was administered with an infusion rate of 0.1 microg kg(-1) min(-1) in a total dose of 12.5 mg starting a minimum of 2 h prior to surgery. Haemodynamic parameters were obtained at baseline and at 4, 8, 12, 16, 20, 24, 28, 36 and 48 h after start of levosimendan. B-type natriuretic peptide was measured on admission and after 48 h. RESULTS: Patients were 86 +/- 7 yr (mean +/- SD) of age. Levosimendan significantly increased cardiac index from 2.4 +/- 0.3 L min(-1) m(-2) at baseline to 3.2 +/- 0.6 L min(-1) m(-2) after 24 h by increases in stroke volume index (baseline 27 +/- 5 mL m(-2), after 24 h 37 +/- 10 mL m(-2), P < 0.05). Systemic vascular resistance index significantly decreased from 2718 +/- 841 to 1964 +/- 385 dyn s cm-5 m(-2) within 24 h. Haemodynamic changes exerted by levosimendan persisted up to 48 h. B-type natriuretic peptide plasma concentrations decreased from 1143 +/- 792 to 935 +/- 724 ng L(-1) after 48 h (P = 0.006). CONCLUSION: In patients with heart failure, preoperative start of levosimendan infusion improves intraoperative and postoperative haemodynamics. These findings suggest that levosimendan is a useful drug for preoperative optimization of cardiac function in high-risk patients undergoing major surgery.

Core and skin surface temperature course after normothermic and hypothermic cardiopulmonary bypass and its impact on extubation time.

BACKGROUND AND OBJECTIVE: Cardiopulmonary bypass is associated with temperature pertubations that influence extubation time. Common extubation criteria demand a minimum value of core temperature only. The aim of this prospective study was to test the hypothesis that changes in core and skin surface temperature are related to extubation time in patients following normothermic and hypothermic cardiopulmonary bypass. METHODS: Forty patients undergoing cardiac surgery were studied; 28 patients had normothermic cardiopulmonary bypass (nasopharyngeal temperature >35.5 degrees C) and 12 had hypothermic cardiopulmonary bypass (28-34 degrees C). In the intensive care unit, urinary bladder temperature and skin surface temperature gradient (forearm temperature minus fingertip temperature: >0 degrees C = vasoconstriction, < or =0 degrees C = vasodilatation) were measured at 30-min intervals for 10 h postoperatively. At the same intervals, the patients were evaluated for extubation according to common extubation criteria. RESULTS: On arrival in the intensive care unit the mean urinary bladder temperature was 36.8 +/- 0.5 degrees C in the normothermic group and 36.4+/-0.3 degrees C in the hypothermic group (P = 0.014). The skin surface temperature gradient indicated severe vasoconstriction in the both groups. The shift from vasoconstriction to vasodilatation was faster in normothermic cardiopulmonary bypass patients (138+/-65 min) than in patients after hypothermic cardiopulmonary bypass (186+/-61 min, P = 0.034). There was a linear relation between the time to reach a skin surface temperature gradient = 0 degrees C and extubation time (r2 = 0.56, normothermic group; r2 = 0.82, hypothermic group). CONCLUSIONS: The transition from peripheral vasoconstriction to vasodilatation is related to extubation time in patients following cardiac surgery under normothermic as well as hypothermic cardiopulmonary bypass.

Influence of cumulative number of marginal donor criteria on primary organ dysfunction in liver recipients.

BACKGROUND: The aim of this cohort study was to assess the cumulative effect of marginal donor criteria on initial graft function and patient survival after liver transplantation. METHODS: We included 734 consecutive patients who underwent orthotopic liver transplantation at the Vienna General Hospital between January 1993 and December 2003. We employed the local registry of the Department of Transplant Surgery, where variables of all patients are routinely and prospectively recorded. Primary outcome was initial graft function, secondary outcome was patient survival. RESULTS: Cumulative number of marginal donor criteria was significantly and linearly associated with an increased rate of primary dysfunction (PDF; p = 0.005). In patients with more than three cumulative marginal donor criteria the rate of PDF was 36%. Patient survival was not influenced by the cumulative number of donor criteria (log-rank test, p = 0.81). Independent marginal donor criteria to predict PDF were cold ischemia time >10 h [odds ratio (OR) 0.56; 95% CI 0.32-0.98] and donor peak serum sodium >155 mEq/L (OR 0.44; 95% CI 0.26-0.77), as assessed in a multivariate regression model. CONCLUSIONS: The use of marginal liver donors with more than three marginal donor criteria shows deleterious effects on initial graft function. Noteworthy, patient survival was not associated with marginal donor criteria, which may be explained by early and successful retransplantation of liver recipients with primary non-function.

The use of the novel calcium sensitizer levosimendan in critically ill patients.

Levosimendan, a novel calcium sensitizer, enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilation. In this prospective observational study the haemodynamic effects of levosimendan in postoperative critically ill patients are reported. Twelve patients with the need for inotropic support were studied. One dose of levosimendan (12.5 mg) was administered at a rate of 0.1-0.2 microg kg(-1).min(-1), either alone or in addition to pre-existing inotropic therapy. Haemodynamic measurements were obtained at baseline, and at 3 h, 6 h, 12 h, and 24 h after the start of the levosimendan infusion. Levosimendan significantly increased cardiac output from (mean+/-SD) 4.3+/-0.91.min(-1) to 5.2+/-1.51 min(-1) after 24h (P=0.013), by increases in stroke volume (baseline 47+/-15 ml, after 24h 57+/-25 ml, P=0.05), as heart rate remained unchanged. Systemic vascular resistance decreased from 1239+/-430 dyn.sec.cm(-5) at baseline to 963+/-322 dyn.sec. cm(-5) at 24h (P<0.001). Pre-existing inotropic therapy present in ten patients remained unchanged or was reduced. In postoperative critically ill patients, infusion of levosimendan exerted favourable haemodynamic responses. Levosimendan increased cardiac output by increasing stroke volume, which might be attributed primarily to its inotropic properties. Due to its cyclic adenosine monophosphate independent positive inotropic effects, levosimendan may be of value as adjunctive therapy to other inotropic drugs in critically ill patients.

[Variants of inborn errors of metabolism with late onset but nevertheless life threatening course]. / Varianten angeborener Stoffwechselstörungen mit spätem Beginn, aber bedrohlichem Verlauf.

BACKGROUND: There is a growing number of inborn errors of metabolism (IEM) with late onset but nevertheless life threatening course. PATIENTS: Patients with late onset variants of urea cycle defects, fatty acid oxidation defects and organic acidurias are demonstrated. METHODS: Biochemical, enzymatic, molecular methods and especially tandem mass spectrometry (TMS) are used for diagnostic purposes. RESULTS: IEM variants with late onset are difficult to be detected. TMS has some advantages as the simple sampling of dried blood on filter paper cards and the simultaneous detection of a broad spectrum of disturbances in amino acids and acylcarnitines. This may facilitate a prompt diagnosis. Asymptomatic persons not only carry an unrecognized risk for severe metabolic decompensation but also pass on their mutation of IEM and the associated disease risk to the next generation (Non-disease). CONCLUSION: TMS, which is used in newborn screening centers is very convenient to establish a prompt diagnosis in some unexpected late onset metabolic crisis following surgeries, infections or other catabolic stress. Furthermore TMS may be a suitable and rapid adjunct method to improve transplantation management.

Can hypocapnia reduce cerebral embolization during cardiopulmonary bypass?

BACKGROUND: Cerebral embolization is a major cause of central nervous dysfunction after cardiopulmonary bypass. Experimental studies demonstrate that reductions in arterial carbon dioxide tension (PaCO2) can reduce cerebral embolization during cardiopulmonary bypass. This study examined the effects of brief PaCO2 manipulations on cerebral embolization in patients undergoing cardiac valve procedures. METHODS: Patients were prospectively randomized to either hypocapnia (PaCO2 = 30 to 32 mm Hg, n = 30) or normocapnia (PaCO2 = 40 to 42 mm Hg, n = 31) before aortic cross-clamp removal. With removal of the aortic cross-clamp embolic signals were recorded by transcranial Doppler ultrasonography for the next 15 minutes. RESULTS: Despite significant differences in PaCO2, groups did not differ statistically in total cerebral emboli counts. The mean number of embolic events was 107 +/- 100 (median, 80) in the hypocapnic group and 135 +/- 115 (median, 96) in the normocapnic group, respectively (p = 0.315). CONCLUSIONS: Due to the high between-patient variability in embolization, reductions in PaCO2 did not result in a statistically significant decrease in cerebral emboli. In contrast to experimental studies, the beneficial effect of hypocapnia on cerebral embolization could not be demonstrated in humans.

Multiorgan donation from a donor with unrecognized ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency, the most common inherited urea cycle disorder, shows a spectrum of severity ranging from severe neonatal hyperammonemic coma to no symptoms among adults. We report on the multiorgan procurement from a donor who died of cerebral edema due to unrecognized late-onset OTC deficiency. The donor's OTC deficiency was diagnosed retrospectively since the liver graft recipient developed cerebral edema postoperatively due to hyperammonemia. Plasma ammonia was extremely elevated (3793 micromol/l), but was not accompanied by general liver dysfunction. Post mortem, the diagnosis of OTC deficiency was established by enzyme and molecular analysis in a biopsy of the transplanted liver. In contrast to the fatal course of the liver graft recipient, the kidney, lung, and heart transplantations were successful. Ten months after transplantation these recipients were alive and showed good graft function. This case demonstrates the importance of careful donor evaluation, particularly if the donor's cause of death is obscure.

Comparing Doppler ultrasonography and cerebral oximetry as indicators for shunting in carotid endarterectomy.

To determine the thresholds of selective shunting in carotid endarterectomy during general anesthesia, we compared transcranial Doppler ultrasonography and cerebral oximetry (RSO2). During carotid cross-clamping, RSO2 and mean blood flow velocity in the middle cerebral artery (Vm,mca) was simultaneously monitored in 55 of 59 patients. A relative decrease in Vm,mca to <20% of preclamp velocity was the indication for selective shunting. Three patients were shunted, two because of criteria of Vm,mca and one in which Vm,mca measurements were impossible. No postoperative neurological deficits occurred. During cross-clamping, both Vm,mca (42+/-16 vs. 26+/-12 cm/s; P<0.001) and RSO2 (68+/-7% vs. 62+/-8%; P<0.01) decreased and a significant correlation between %Vm,mca and DeltaRSO2 was found (R(2) = 0.40; P = 0.003). Decreases in RSO2 >13% identified two patients later shunted; however, this threshold would have indicated unnecessary shunting in seven patients (false positives = 17%). Transcranial Doppler ultrasonography identified patients at risk for ischemia more accurately than RSO2. Relying on RSO2 alone would increase the number of unnecessary shunts because of the low specificity. Accepting higher decreases in RSO2 does not appear reasonable because it bears the risk of a low sensitivity.

Intrathoracic fluid volumes and pulmonary function during orthotopic liver transplantation.

BACKGROUND: Impaired pulmonary function is a frequent finding in patients undergoing orthotopic liver transplantation (OLT). Experimental data suggest an essential contribution of splanchnic ischemia and reperfusion as a result of intraoperative volume shifts, i.e., the accumulation of extravascular lung water (EVLW). Increases of intrathoracic blood volume (ITBV) and pulmonary blood volume (PBV) might additionally influence pulmonary capillary fluid filtration. The main objective of this study was to determine the intrathoracic volume changes during OLT and to test whether there were any relationships between intra- and extravascular volume shifts and pulmonary function, as determined by the calculation of venous admixture (QS/QT) and alveolar-arterial oxygen gradient (AaDO2). METHODS: Twenty-five patients undergoing OLT were studied. Using the transpulmonary double indicator dilution method, ITBV, PBV, and EVLW were determined from the mean transit times and exponential decay times of the indocyanine green and the thermal indicator curves recorded simultaneously with a fiberoptic catheter in the descending aorta. Recordings were made after induction of anesthesia, at the end of the anhepatic stage, immediately after reperfusion, and 1 and 4 h postoperatively. RESULTS: Significant increases in QS/QT related to changes of ITBV were observed after reperfusion. Only a minor impact on AaDO2 was perceived. EVLW remained constant during the study period. CONCLUSIONS: Postreperfusion increases of ITBV influence pulmonary function, as demonstrated by the increase in QS/QT. However, they need not be associated with greater EVLW levels, and impact on oxygenation is less severe than assumed. Hence, sufficient mechanisms protecting oxygenation and stalling increased EVLW seem to be present during uncomplicated human OLT.

S(+)-ketamine for caudal block in paediatric anaesthesia.

We have evaluated the intra- and postoperative analgesic efficacy of preservative-free S(+)-ketamine compared with bupivacaine for caudal block in paediatric hernia repair. After induction of general anaesthesia, 49 children undergoing hernia repair were given a caudal injection (0.75 ml kg-1) of S(+)-ketamine 0.5 mg kg-1 (group K1), S(+)-ketamine 1.0 mg kg-1 (group K2) or 0.25% bupivacaine with epinephrine 1:200,000 (group B). No additional analgesic drugs were required during operation in any of the groups. Haemodynamic and respiratory variables remained stable during the observation period. Mean duration of analgesia was significantly longer in groups B and K2 compared with group K1 (300 (SD 96) min and 273 (123) min vs 203 (117) min; P < 0.05). Groups B and K2 required less analgesics in the postoperative period compared with group K1 (30% and 33% vs 72%; P < 0.05). Postoperative sedation scores were comparable between the three groups. We conclude that S(+)-ketamine 1.0 mg kg-1 for caudal block in children produced surgical and postoperative analgesia equivalent to that of bupivacaine.

Effect of temperature and PaCO2 on cerebral embolization during cardiopulmonary bypass in swine.

BACKGROUND: Patients experience cerebral embolization during cardiopulmonary bypass (CPB). This study determined if alterations in temperature and/or PaCO2 can reduce cerebral and ocular embolization. METHODS AND RESULTS: Forty-four pigs underwent CPB: 24 animals at 28 degrees C, and 20 at 38 degrees C. The two temperature groups were randomized to undergo embolization (67-microm fluorescent microspheres) at either hypercarbia or hypocarbia. Before and after embolization, cerebral and ocular blood flow were determined at normocarbia. Reducing temperature or PaCO2 reduced cerebral and ocular embolization. Hypocarbia reduced cerebral embolization by 60% and 45% in normothermic and hypothermic groups, respectively (p < 0.0001 and p < 0.05). Relative to normothermic animals, hypothermia reduced cerebral embolization by 37% under an elevated CO2 condition (p < 0.05), but not under hypocarbic conditions. Similarly, regardless of temperature, fewer emboli were delivered to the eye in hypocarbic animals (p < 0.05), but hypothermia did not reduce ocular embolization. CONCLUSIONS: Cerebral embolization is determined by both temperature and PaCO2 at the time of embolization. In CPB practice, reductions in temperature and/or PaCO2 during periods of embolic risk may reduce brain injury.

Relationship between cardiopulmonary bypass flow rate and cerebral embolization in dogs.

BACKGROUND: Cerebral embolization is a primary cause of cardiac surgical neurologic morbidity. During cardiopulmonary bypass (CPB), there are well-defined periods of embolic risk. In theory, cerebral embolization might be reduced by an increase in pump flow during these periods. The purpose of this study was to determine the CPB flow-embolization relation in a canine model. METHODS: Twenty mongrel dogs underwent CPB at 35 degrees C with alpha-stat management and a fentanyl-midazolam anesthetic. In each animal, CPB flow was adjusted to achieve a mean arterial pressure of 65-75 mmHg. During CPB, an embolic load of 1.2 x 10(5) 67 microm fluorescent microspheres was injected into the arterial inflow line. Before and after embolization, cerebral blood flow was determined using 15-microm microspheres. Tissue was taken from 12 brain regions and microspheres were recovered. The relation between pump flow and embolization/g of brain was determined. RESULTS: The mean arterial pressure at embolization was 67 +/-4 mmHg, and the range of pump flow was 0.9-3.5 l x min(-1)x m(-2). Cerebral blood flow was independent of pump flow. At lower pump flow, the percentage of that flow delivered to the brain increased. There was a strong inverse relation between pump flow and cerebral embolization (r = -0.708, P < 0.000 by Spearman rank order correlation). CONCLUSIONS: Cerebral embolization is determined by the CPB flow. At an unchanged mean arterial pressure, as pump flow is reduced, a progressively greater proportion of that flow is delivered to the brain.

[Difference between gastric mucosal pCO2 and arterio-intramucosal pCO2 during orthotopic liver transplantation]. / Magenmukosa-pCO2 und arterio-intramukosale pCO2-Differenz während orthotoper Lebertransplantation.

Tonometry is a clinically accepted method to monitor blood flow of the splanchnic region, which is of particular interest in orthotopic liver transplantation (OLT). We investigated the hemodynamic changes and the tonometrically registered perioperative course of the difference between gastric mucosal pCO2 (prCO2) and arterial mucosal CO2 (CO2 gap) in 23 patients undergoing OLT without veno-venous bypass. Gastric mucosal pH (pHi) was additionally calculated. Despite significant changes in systemic hemodynamics during the anhepatic stage and after reperfusion and a significant drop in pHi during anhepacy, the difference between prCO2 and CO2 was constant. These contrasting findings of tonometry, i.e. solely a drop in pHi is, in our opinion, a consequence of the poor metabolic capacity of the liver in the perioperative OLT period, which influenced the calculation of the pHi with the Henderson-Hasselbalch equation. We conclude that, due to methodical problems, calculated pHi is not a reliable indicator of splanchnic blood flow and oxygenation during OLT. We therefore suggest that the prCO2 and the CO2 gap be used to monitor the splanchnic region. These parameters, obtained perioperatively, do not indicate a further reduction in splanchnic oxygenation despite profound changes in systemic hemodynamics during OLT without veno-venous bypass.

Support of mean arterial pressure during tepid cardiopulmonary bypass: effects of phenylephrine and pump flow on systemic oxygen supply and demand.

OBJECTIVE: To examine the effects of phenylephrine infusion and increases in pump flow on systemic oxygen supply and demand when they are used to support mean arterial pressure (MAP) during cardiopulmonary bypass (CPB). DESIGN: Prospective, unblinded study. SETTING: The animal cardiopulmonary laboratory at the Mayo Foundation (Rochester, MN). PARTICIPANTS: Twelve pigs. INTERVENTIONS: Twelve pigs had systemic oxygen delivery (DO2) and consumption (VO2) measured before CPB and then underwent CPB at 35 degrees C. During CPB, measurements of DO2 and VO2 were obtained at an MAP of approximately 50 mmHg and a pump flow of 2.2 L/min/m2. Thereafter, MAP was elevated to 70 mmHg either by increases in pump flow or by a phenylephrine infusion, and the balance between systemic oxygen supply and demand was reassessed. MEASUREMENTS AND MAIN RESULTS: Before CPB, DO2 was 375 +/- 83 mL/min/m2 and decreased with the onset of CPB mainly because of the effects of hemodilution. During CPB, with a pump flow of 2.2 L/min/m2 and an MAP of 53 mmHg, DO2 was 218 +/- 40 mL/min/m2. Increasing perfusion pressure to an MAP of 72 mmHg with phenylephrine and maintaining pump flow constant (2.2 L/min/m2) did not change DO2 (222 +/- 37 mL/min/m2), and the oxygen extraction ratio (OER) was increased relative to pre-CPB levels. In contrast, increasing MAP to 71 mmHg by increasing pump flow to 3.2 L/min/m2 resulted in a significantly greater DO2, and the OER normalized to the pre-CPB value. CONCLUSIONS: During CPB with conventional flow rates, DO2 is decreased. Supporting MAP with increases in pump flow better maintains DO2 than the administration of an alpha-agonist.

The use of the antioxidant tirilazad mesylate in human liver transplantation: is there a therapeutic benefit?

OBJECTIVES: To test the hypothesis whether in patients undergoing liver transplantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia-reperfusion injury and improve postoperative outcome. DESIGN: Prospective, randomised, placebo controlled trial. SETTING: University hospital. PATIENTS: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). INTERVENTIONS: Patients in the tirilazad group (n = 10) received four intravenous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/kg) after the induction of anaesthesia. The other patients (n = 10) served as controls. MEASUREMENTS AND RESULTS: Plasma levels of malonaldehyde (MDA) were determined after the induction of anaesthesia prior to the infusion of tirilazad (baseline), during the anhepatic period, and 5 min and 24 h after reperfusion. Postoperatively, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change during the anhepatic period and after reperfusion and they did not differ between groups. Postoperative liver enzymes and prothrombin time did not differ between groups, but on the first (p = 0.03) and second (p = 0.01) postoperative day cholinesterase levels were significantly higher in tirilazad-treated patients than in control patients. For neither length of stay in the intensive care unit nor hospital stay were any differences observed between groups. CONCLUSIONS: In patients undergoing liver transplantation, tirilazad does not improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earlier recovery of liver function remains to be tested.

Cerebral response to haemodilution during cardiopulmonary bypass in dogs: the role of nitric oxide synthase.

During cardiopulmonary bypass, haemodilution is standard practice and is accompanied by increases in cerebral blood flow (CBF). We investigated if changes in cerebral vascular resistance (CVR) during cardiopulmonary bypass-haemodilution are dependent on nitric oxide synthase. The cerebral response to haemodilution in nine dogs treated with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), was compared with a control group (n = 8). Both groups underwent serial isovolaemic haemodilution (target packed cell volumes 0.39, 0.26, 0.19 and 0.14) using 6% dextran 70. CBF, CVR and cerebral metabolic rate for oxygen (CMRO2) were measured. While initial CVR was different in the two groups, haemodilution-dependent reductions in CVR were equivalent and the curves describing the packed cell volume-CVR relationship were parallel in control and nitric oxide synthase inhibition groups. Our data indicate that nitric oxide synthase does not play a primary role in the cerebral response to haemodilution.