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.

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.

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.

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.

Quantification and distribution of cerebral emboli during cardiopulmonary bypass in the swine: the impact of PaCO2.

BACKGROUND: Patients undergoing cardiac surgery have a substantial incidence of neurologic complications related to cerebral embolization during cardiopulmonary bypass. The purpose of this study was to determine if adjustments in the arterial carbon dioxide (PaCO2) level can reduce cerebral and ocular embolization. METHODS: Twenty pigs underwent cardiopulmonary bypass at 38 degrees C. At either hypercarbia (PaCO2 = 50-55 mmHg, group H, n = 10) or hypocarbia (PaCO2 = 25-30 mmHg, group L, n = 10), an embolic load of 1.2 x 10(50 67-microm orange fluorescent microspheres was injected into the aortic cannula. Before and after embolization, cerebral and ocular blood flows were determined at normocapnia using 15-microm fluorescent microspheres. After cardiopulmonary bypass was completed, the eyes were enucleated and brain tissue samples were collected. Microspheres were isolated and the fluorescence was measured. RESULTS: In groups H and L, the mean PaCO2 values at embolization were 52+/-3 mmHg and 27+/-2 mmHg, respectively (P < 0.0001). Total and regional embolization were significantly less in hypocapnia than in hypercapnic animals: 142% more emboli were detected in the brain in group H than in group L (P < 0.0001). Cerebral blood flow after embolization was unchanged in both groups. Similarly, fewer ocular emboli occurred in hypocapnic animals than in hypercapnic animals (P = 0.044), but in contrast to the brain, ocular blood flow decreased significantly in both groups after embolization. CONCLUSIONS: Cerebral embolization is determined by the PaCO2 at the time of embolization. In cardiopulmonary bypass practice, reductions in PaCO2 during periods of embolic risk may reduce the risk for brain injury.

Supralaryngeal tubeless combined high-frequency jet ventilation for laser surgery of the larynx and trachea.

We have developed a new technique of combined high-frequency jet ventilation (HFJV), characterized by simultaneous application of a low-frequency (LF) and a high-frequency (HF) jet stream. Tubeless supralaryngeal jet ventilation was delivered via a modified Kleinsasser laryngoscope. We studied 44 adults undergoing 45 elective surgical procedures of the larynx and trachea using a carbon dioxide laser during HFJV. Applied inspiratory oxygen ratios ranged from 0.4 to 1.0. Mean driving pressures of the HF and LF jet streams were 1.5 bar and 1.8 bar in adults, respectively. Mean duration of HFJV was 41 (range 10-180) min. HFJV resulted in mean PaO2 and PaCO2 values of 16.6 (range 9.8-26.9) kPa and 5.7 (3.0-7.6) kPa, respectively. Tubeless supralaryngeal HFJV was safe and effective in maintaining gas exchange in the presence of laryngeal or tracheal stenoses, providing optimal visibility of anatomical structures, offering maximum space for surgical manipulation, and avoiding the use of combustible material inside the larynx or trachea.

Critical cerebral perfusion pressure during tepid heart operations in dogs.

BACKGROUND: The management of blood pressure during cardiopulmonary bypass varies widely. This may be particularly relevant with the trend to warmer bypass temperatures and an older patient population. Therefore, we examined the minimal perfusion pressure that maintains cerebral oxygen delivery during cardiopulmonary bypass at 33 degrees C. METHODS: Ten dogs were placed on bypass and body temperature was reduced to 33 degrees C (alpha-stat pH management). At six randomly ordered mean arterial blood pressures (35, 40, 45, 50, 60, and 70 mm Hg), cerebral blood flow, oxygen delivery, and metabolic rate were determined. RESULTS: Cerebral oxygen delivery was stable if the mean arterial pressure was greater than or equal to 60 mm Hg. If mean arterial pressure was less than or equal to 50 mm Hg, cerebral oxygen delivery decreased, and at less than 45 mm Hg cerebral ischemia was seen. CONCLUSIONS: In a dog without vascular disease, the brain becomes perfusion pressure-dependent at a mean arterial pressure of approximately 50 mm Hg. There is no leftward shift of the cerebral autoregulatory curve during bypass at 33 degrees C. Greater support of mean arterial pressure during "tepid" cardiopulmonary bypass is indicated in the current adult surgical population that is older and has vascular comorbidity.

Hemodilution and whole body oxygen balance during normothermic cardiopulmonary bypass in dogs.

OBJECTIVE: The purpose of this study was to determine the minimum hematocrit value that can support whole body oxygen consumption during normothermic cardiopulmonary bypass. The effect of hemodilution on peripheral resistance, whole body oxygen delivery, and oxygen consumption was determined over a range of hematocrit values. METHODS: Measurements were obtained during 38 degrees C cardiopulmonary bypass with progressive normovolemic hemodilution (hematocrit value 40% to 9%) in nine dogs. Dextran 70 (6%) was used as a diluent. Anesthesia consisted of high-dose fentanyl and midazolam. A mean arterial pressure of 60 mm Hg was maintained throughout cardiopulmonary bypass via increases in pump flow. RESULTS: Progressive hemodilution was associated with a decreasing total peripheral resistance. During normothermic cardiopulmonary bypass with a whole blood prime, the whole body oxygen consumption approximated values previously reported in dogs under nonbypass conditions. Oxygen delivery and whole body oxygen uptake were maintained between a hematocrit value of 39% and 25%. Significant decreases for both were seen when the hematocrit value was reduced to 18% and below. CONCLUSIONS: A hematocrit level greater than 18% was needed to maintain systemic oxygen delivery and consumption during warm cardiopulmonary bypass. The critical hematocrit value may be higher under bypass than nonbypass conditions because the flow increases that are practical during cardiopulmonary bypass do not approximate those seen in response to hemodilution of the intact circulation. Finally, the critical hematocrit value for the body may be higher than that required for the brain during warm cardiopulmonary bypass.