Linezolid brain penetration in neurointensive care patients.

BACKGROUND: Linezolid exposure in critically ill patients is associated with high inter-individual variability, potentially resulting in subtherapeutic antibiotic exposure. Linezolid exhibits good penetration into the CSF, but its penetration into cerebral interstitial fluid (ISF) is unknown. OBJECTIVES: To determine linezolid penetration into CSF and cerebral ISF of neurointensive care patients. PATIENTS AND METHODS: Five neurocritical care patients received 600 mg of linezolid IV twice daily for treatment of extracerebral infections. At steady state, blood and CSF samples were collected from arterial and ventricular catheters, and microdialysate was obtained from a cerebral intraparenchymal probe. RESULTS: The median fAUC0-24 was 57.6 (24.9-365) mg·h/L in plasma, 64.1 (43.5-306.1) mg·h/L in CSF, and 27.0 (10.7-217.6) mg·h/L in cerebral ISF. The median penetration ratio (fAUCbrain_or_CSF/fAUCplasma) was 0.5 (0.25-0.81) for cerebral ISF and 0.92 (0.79-1) for CSF. Cerebral ISF concentrations correlated well with plasma (R = 0.93, P < 0.001) and CSF levels (R = 0.93, P < 0.001).The median fAUC0-24/MIC ratio was ≥100 in plasma and CSF for MICs of ≤0.5 mg/L, and in cerebral ISF for MICs of ≤0.25 mg/L. The median fT>MIC was ≥80% of the dosing interval in CSF for MICs of ≤0.5 mg/L, and in plasma and cerebral ISF for MICs of ≤0.25 mg/L. CONCLUSIONS: Linezolid demonstrates a high degree of cerebral penetration, and brain concentrations correlate well with plasma and CSF levels. However, substantial variability in plasma levels, and thus cerebral concentrations, may result in subtherapeutic tissue concentrations in critically ill patients with standard dosing, necessitating therapeutic drug monitoring.

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Nimodipine is routinely administered to aneurysmal subarachnoid hemorrhage patients to improve functional outcomes. Nimodipine can induce marked systemic hypotension, which might impair cerebral perfusion and brain metabolism. METHODS: Twenty-seven aneurysmal subarachnoid hemorrhage patients having multimodality neuromonitoring and oral nimodipine treatment as standard of care were included in this retrospective study. Alterations in mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), brain tissue oxygen tension (pbtO2), and brain metabolism (cerebral microdialysis), were investigated up to 120 minutes after oral administration of nimodipine (60 mg or 30 mg), using mixed linear models. RESULTS: Three thousand four hundred twenty-five oral nimodipine administrations were investigated (126±59 administrations/patient). After 60 mg of oral nimodipine, there was an immediate statistically significant (but clinically irrelevant) drop in MAP (relative change, 0.97; P<0.001) and CPP (relative change: 0.97; P<0.001) compared with baseline, which lasted for the whole 120 minutes observation period (P<0.001). Subsequently, pbtO2 significantly decreased 50 minutes after administration (P=0.04) for the rest of the observation period; the maximum decrease was -0.6 mmHg after 100 minutes (P<0.001). None of the investigated cerebral metabolites (glucose, lactate, pyruvate, lactate/pyruvate ratio, glutamate, glycerol) changed after 60 mg nimodipine. Compared with 60 mg nimodipine, 30 mg induced a lower reduction in MAP (relative change, 1.01; P=0.02) and CPP (relative change, 1.01; P=0.03) but had similar effects on pbtO2 and cerebral metabolism (P>0.05). CONCLUSIONS: Oral nimodipine reduced MAP, which translated into a reduction in cerebral perfusion and oxygenation. However, these changes are unlikely to be clinically relevant, as the absolute changes were minimal and did not impact cerebral metabolism.

Meropenem Population Pharmacokinetics and Simulations in Plasma, Cerebrospinal Fluid, and Brain Tissue.

Meropenem is a broad spectrum carbapenem used for the treatment of cerebral infections. There is a need for data describing meropenem pharmacokinetics (PK) in the brain tissue to optimize therapy in these infections. Here, we present a meropenem PK model in the central nervous system and simulate dosing regimens. This was a population PK analysis of a previously published prospective study of patients admitted to the neurointesive care unit between 2016 and 2019 who received 2 g of meropenem intravenously every 8 h. Meropenem concentration was determined in blood, cerebrospinal fluid (CSF), and brain microdialysate. Meropenem was described by a six-compartment model: two compartments in the blood, two in the CSF, and two in the brain tissue. Creatinine clearance and brain glucose were included as covariates. The median elimination rate constant was 1.26 h-1, the central plasma volume was 5.38 L, and the transfer rate constants from the blood to the CSF and from the blood to the brain were 0.001 h-1 and 0.02 h-1, respectively. In the first 24 h, meropenem 2 g, administered every 8 h via intermittent and extended infusions achieved good target attainment in the CSF and brain, but continuous infusion (CI) was better at steady-state. Administering a 3 g loading dose (LD) followed by 8 g CI was beneficial for early target attainment. In conclusion, a meropenem PK model was developed using blood, CSF, and brain microdialysate samples. An 8 g CI may be needed for good target attainment in the CSF and brain. Giving a LD prior to the CI improved the probability of early target attainment.

The Effect of Pregabalin on the Minimum Alveolar Concentration of Sevoflurane: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

Background: Pregabalin is commonly used perioperatively to reduce post-operative pain and opioid consumption and to prevent the development of chronic pain. It has been shown to reduce anesthetic consumption in balanced anesthesia, but studies investigating its effect on the minimum alveolar concentration (MAC) of volatile anesthetics are lacking. The aim of this study was to investigate the effect of two different doses of pregabalin on the MAC of sevoflurane. Methods: In a randomized, double-blinded, placebo controlled clinical study, 75 patients were assigned to receive placebo, 300 mg pregabalin, or 150 mg pregabalin, as a capsule 1 h before anesthesia induction with sevoflurane only. After equilibration, the response to skin incision (movement vs. non-movement) was monitored. The MAC was assessed using an up- and down-titration method. Results: The MAC of sevoflurane was estimated as 2.16% (95% CI, 2.07-2.32%) in the placebo group, 1.44% (95% CI, 1.26-1.70%) in the 300 mg pregabalin group, and 1.81% (95% CI, 1.49-2.13%) in the 150 mg pregabalin group. We therefore report a 33% reduction in the MAC of sevoflurane in the 300 mg pregabalin group as compared to placebo. The MAC of the 150 mg pregabalin group was reduced by 16% as compared to placebo but was not statistically significant. Conclusions: The administration of 300 mg pregabalin reduced the MAC of sevoflurane by 33%, while the administration of 150 mg pregabalin did not significantly reduce the MAC of sevoflurane. Pregabalin use led to a small reduction in post-operative pain levels but increased side effects in a dose-dependent manner.

Ethanol reduces the minimum alveolar concentration of sevoflurane in rats.

A high number of trauma patients are under the influence of alcohol. Since many of them need immediate surgical procedures, it is imperative to be aware of the interaction of alcohol with general anesthesia. To counter challenges that arise from clinical studies, we designed an animal experiment in which 48 adult Wistar rats either received 1 g · kg-1 ethanol, 2 g · kg-1 ethanol or placebo via intraperitoneal application. Subsequently, they were anesthetized with an individual concentration of sevoflurane. The minimum alveolar concentration (MAC) of the different groups was assessed using Dixon's up-and-down design and isotonic regression methods. The bootstrap estimate of the MAC of sevoflurane in the placebo group was 2.24 vol% (95% CI 1.97-2.94 vol%). In the low dose ethanol group, the bootstrap estimate was 1.65 vol% (95% CI 1.40-1.98 vol%), and in the high dose ethanol group, it was 1.08 vol% (95% CI 0.73-1.42 vol%). We therefore report that intraperitoneal application of 1 g · kg-1 or 2 g · kg-1 ethanol both resulted in a significant reduction of the MAC of sevoflurane in adult Wistar rats: by 26.3% and 51.8% respectively as compared to placebo.

Brain Tissue Oxygen Response as Indicator for Cerebral Lactate Levels in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Early detection of cerebral ischemia and metabolic crisis is crucial in critically ill subarachnoid hemorrhage (SAH) patients. Variable increases in brain tissue oxygen tension (PbtO2) are observed when the fraction of inspired oxygen (FiO2) is increased to 1.0. The aim of this prospective study was to evaluate whether a 3-minute hyperoxic challenge can identify patients at risk for cerebral ischemia detected by cerebral microdialysis. METHODS: Twenty consecutive severe SAH patients undergoing continuous cerebral PbtO2 and microdialysis monitoring were included. FiO2 was increased to 1.0 for 3 minutes (the FiO2 challenge) twice a day and PbtO2 responses during the FiO2 challenges were related to cerebral microdialysis-measures, ie, lactate, the lactate-pyruvate ratio, and glycerol. Multivariable linear and logistic regression models were created for each outcome parameter. RESULTS: After predefined exclusions, 274 of 400 FiO2 challenges were included in the analysis. Lower absolute increases in PbtO2 (∆PbtO2) during FiO2 challenges were significantly associated with higher cerebral lactate concentration (P<0.001), and patients were at higher risk for ischemic lactate levels >4 mmol/L (odds ratio 0.947; P=0.04). Median (interquartile range) ∆PbtO2 was 7.1 (4.6 to 12.17) mm Hg when cerebral lactate was >4 mmol/L and 10.2 (15.76 to 14.24) mm Hg at normal lactate values (≤4 mmol/L). Median ∆PbtO2 was significantly lower during hypoxic than during hyperglycolytic lactate elevations (4.6 vs. 10.6 mm Hg, respectively; P<0.001). Lactate-pyruvate ratio and glycerol levels were mainly determined by baseline characteristics. CONCLUSIONS: A 3-minute FiO2 challenge is an easy to perform and feasible bedside diagnostic tool in SAH patients. The absolute increase in PbtO2 during the FiO2 challenge might be a useful surrogate marker to estimate cerebral lactate concentrations and might be used to identify patients at risk for impending ischemia.

Meropenem concentrations in brain tissue of neurointensive care patients exceed CSF levels.

BACKGROUND: Inadequate antibiotic exposure in cerebral infections might have detrimental effects on clinical outcome. Commonly, antibiotic concentrations within the CSF were used to estimate cerebral target levels. However, the actual pharmacological active unbound drug concentration beyond the blood-brain barrier is unknown. OBJECTIVES: To compare meropenem concentrations in blood, CSF and cerebral microdialysate of neurointensive care patients. PATIENTS AND METHODS: In 12 patients suffering subarachnoid haemorrhage, 2000 mg of meropenem was administered every 8 h due to an extracerebral infection. Meropenem concentrations were determined in blood, CSF and cerebral microdialysate at steady state (n = 11) and following single-dose administration (n = 5). RESULTS: At steady state, the free AUC0-8 was 233.2 ± 42.7 mg·h/L in plasma, 7.8 ± 1.9 mg·h/L in CSF and 26.6 ± 14.0 mg·h/L in brain tissue. The brain tissue penetration ratio (AUCbrain/AUCplasma) was 0.11 ± 0.06, which was more than 3 times higher than in CSF (0.03 ± 0.01), resulting in an AUCCSF/AUCbrain ratio of 0.41 ± 0.16 at steady state. After single-dose administration similar proportions were achieved (AUCbrain/AUCplasma = 0.09 ± 0.08; AUCCSF/AUCplasma = 0.02 ± 0.00). Brain tissue concentrations correlated well with CSF concentrations (R = 0.74, P < 0.001), but only moderately with plasma concentrations (R = 0.51, P < 0.001). Bactericidal thresholds were achieved in both plasma and brain tissue for MIC values ≤16 mg/L. In CSF, bactericidal effects were only reached for MIC values ≤1 mg/L. CONCLUSIONS: Meropenem achieves sufficient bactericidal concentrations for the most common bacterial strains of cerebral infections in both plasma and brain tissue, even in non-inflamed brain tissue. CSF concentrations would highly underestimate the target site activity of meropenem beyond the blood-brain barrier.

Detrimental effects of intrahospital transport on cerebral metabolism in patients suffering severe aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Intrahospital transport for CT scans is routinely performed for neurosurgical patients. Particularly in the sedated and mechanically ventilated patient, intracranial hypertension and blood pressure fluctuations that might impair cerebral perfusion are frequently observed during these interventions. This study quantifies the impact of intrahospital patient transport on multimodality monitoring measurements, with a particular focus on cerebral metabolism. METHODS: Forty intrahospital transports in 20 consecutive patients suffering severe aneurysmal subarachnoid hemorrhage (SAH) under continuous intracranial pressure (ICP), brain tissue oxygen tension (pbtO2), and cerebral microdialysis monitoring were prospectively included. Changes in multimodality neuromonitoring data during intrahospital transport to the CT scanner and the subsequent 10 hours were evaluated using linear mixed models. Furthermore, the impact of risk factors at transportation, such as cerebral vasospasm, cerebral hypoxia (pbtO2 < 15 mm Hg), metabolic crisis (lactate-pyruvate ratio [LPR] > 40), and transport duration on cerebral metabolism, was analyzed. RESULTS: During the transport, the mean ICP significantly increased from 7.1 ± 3.9 mm Hg to 13.5 ± 6.0 mm Hg (p < 0.001). The ICP exceeded 20 mm Hg in 92.5% of patients; pbtO2 showed a parallel rise from 23.1 ± 13.3 mm Hg to 28.5 ± 23.6 mm Hg (p = 0.02) due to an increase in the fraction of inspired oxygen during the transport. Both ICP and pbtO2 returned to baseline values thereafter. Cerebral glycerol significantly increased from 71.0 ± 54.9 µmol/L to 75.3 ± 56.0 µmol/L during the transport (p = 0.01) and remained elevated for the following 9 hours. In contrast, cerebral pyruvate and lactate levels were stable during the transport but showed a significant secondary increase 1-8 hours and 2-9 hours, respectively, thereafter (p < 0.05). However, the LPR remained stable over the entire observation period. Patients with extended transport duration (more than 25 minutes) were found to have significantly higher levels of cerebral pyruvate and lactate as well as lower glutamate concentrations in the posttransport period. CONCLUSIONS: Intrahospital transport and horizontal positioning during CT scans induce immediate intracranial hypertension and an increase in cerebral glycerol, suggesting neuronal injury. Afterward, sustained impairment of neuronal metabolism for several hours could be observed, which might increase the risk of secondary ischemic events. Therefore, intrahospital transport for neuroradiological imaging should be strongly reconsidered and only indicated if the expected benefit of imaging results outweighs the risks of transportation.

The effect of oral Δ-9-tetrahydrocannabinol on the minimal alveolar concentration of sevoflurane: A randomised, controlled, observer-blinded experimental study.

BACKGROUND: Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated. OBJECTIVE: To investigate the effect of THC on the MAC of sevoflurane in rats. METHODS: Observer-blinded, randomised controlled trial. SETTING: Centre for Biomedical Research of the Medical University of Vienna, 2019. INDIVIDUALS: Thirty-eight adult Wistar rats. INTERVENTIONS: The rats were allocated randomly into one of two groups. Group A received THC 10 mg kg and group B received the corresponding volume of placebo via gastric gavage (administration through a tube placed in the distal oesophagus). The rats were then individually anaesthetised in an airtight sevoflurane-flooded chamber, and the MAC in both groups was determined using Dixon's up-and-down method. Blood samples were drawn to measure serum concentrations of THC. MAIN OUTCOME MEASURES: The primary outcome was the MAC of sevoflurane in Groups A and B. RESULTS: The bootstrap estimate of the MAC of sevoflurane was 2.1 (95% confidence interval 1.8 to 2.4) vol% in the THC group and 2.8 (95% confidence interval 2.7 to 2.9) vol% in the placebo group, corresponding to a significant MAC reduction of 26% in response to THC. CONCLUSION: Gastric administration of THC 10 mg kg significantly reduced the MAC of sevoflurane by 26%. TRIAL REGISTRATION: Not applicable.

Duration of safe apnea in patients with morbid obesity during passive oxygenation using high-flow nasal insufflation versus regular flow nasal insufflation, a randomized trial.

BACKGROUND: Obese patients are at risk for rapid oxygen desaturation during anesthesia induction. Apneic oxygenation with regular flow oxygen insufflation has successfully been used to prolong the duration of safe apnea without desaturation (DAWD) in morbidly obese patients. Using high-flown nasal insufflation of oxygen (HFNI) for apneic oxygenation might further increase the DAWD. OBJECTIVES: To compare the duration of safe apnea using high-flown nasal insufflation of oxygen or standard flow oxygen insufflation for apneic oxygenation in a simulated difficult intubation scenario in patients with morbid obesity. SETTING: Operating room, University Hospital, Austria. METHODS: In a prospective, randomized, clinical trial, patients received standardized preoxygenation and anesthesia induction. Apneic oxygenation was performed using standard nasal prongs (10 L/min) or HFNI (120 L/min) during laryngoscopy. A Cormack-Lehane 3° view was maintained until the oxygen saturation on pulse oximetry (SpO2) dropped ≤95% or for a maximum of 15 minutes. The primary outcome of this study was to compare the duration of safe apnea using HFNI or standard flow oxygen insufflation for apneic oxygenation. In addition, arterial blood gas results, and airway pressures were investigated. RESULTS: In 40 patients with morbid obesity (body mass index [BMI] >40 kg/m2) and the American Society of Anesthesiologists physical classification ≤3 who underwent bariatric surgery, the median duration of safe apnea was 601 (268-900) seconds in the standard group and 537 (399-808) seconds in the HFNI group (P = .698). No differences in arterial blood gas results were observed between the groups. The median airway pressure was 0 (0-0) cm H2O in the standard group and 1 (0-2) cm H2O in the HFNI group (P = .005). CONCLUSION: Compared with standard nasal apneic oxygenation, HFNI did not increase the duration of safe apnea in patients with morbid obesity. A significant but clinically negligible higher airway pressure was observed when using HFNI.

The Impact of Intra-Arterial Papaverine-Hydrochloride on Cerebral Metabolism and Oxygenation for Treatment of Delayed-Onset Post-Subarachnoid Hemorrhage Vasospasm.

BACKGROUND: Delayed posthemorrhagic vasospasm remains among the major complications after aneurysmal subarachnoid hemorrhage (SAH) and can result in devastating ischemic strokes. As rescue therapy, neurointerventional procedures are used for selective vasodilatation. OBJECTIVE: To investigate the effects of intra-arterial papaverine-hydrochloride on cerebral metabolism and oxygenation. METHODS: A total of 10 consecutive patients, suffering from severe aneurysmal SAH were prospectively included. Patients were under continuous multimodality neuromonitoring and required intra-arterial papaverine-hydrochloride for vasospasm unresponsive to hypertensive therapy. Cerebral metabolism (microdialysis), brain tissue oxygen tension (ptiO2), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were analyzed for a period of 12 h following intervention. RESULTS: A median dose of 125 mg papaverine-hydrochloride was administered ipsilateral to the multimodality probe. Angiographic improvement of cerebral vasospasm was observed in 80% of patients. During intervention, a significant elevation of ICP (13.7 ± 5.2 mmHg) and the lactate-pyruvate ratio (LPR) (54.2 ± 15.5) was observed, whereas a decrease in cerebral glucose (0.9 ± 0.5 mmol/L) occurred. Within an hour, an increase of cerebral lactate (5.0 ± 2.0 mmol/L) and glycerol (104.4 ± 89.8 µmol/L) as well as a decrease of glucose (0.9 ± 0.4 mmol/L) were measured. In 2 to 5 h after treatment, the LPR significantly decreased (pretreatment: 39.3 ± 15.3, to lowest 30.5 ± 6.7). Cerebral pyruvate levels increased in 1 to 10 h (pretreatment: 100.1 ± 33.1 µmol/L, to highest 141.4 ± 33.7 µmol/L) after intervention. No significant changes in ptiO2 or CPP occurred. CONCLUSION: The initial detrimental effects of the endovascular procedure itself were outweighed by an improved cerebral metabolism within 10 h thereafter. As the effect was very limited, repeated interventions or continuous application should be considered.

Urinary [TIMP-2] × [IGFBP-7] for predicting acute kidney injury in patients undergoing orthotopic liver transplantation.

BACKGROUND: The product of the concentrations of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (urinary [TIMP-2] × [IGFBP-7]) has been suggested as biomarker for early detection of acute kidney injury (AKI) in various clinical settings. However, the performance of urinary [TIMP-2] × [IGFBP-7] to predict AKI has never been assessed in patients undergoing orthotopic liver transplantation (OLT). Thus, the aim of this study was to assess the early predictive value of urinary [TIMP-2] × [IGFBP-7] for the development of AKI after OLT. METHODS: In this observational study, urinary [TIMP-2] × [IGFBP-7] was measured in samples from adult OLT patients. AKI was diagnosed and classified according to KDIGO criteria. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of urinary [TIMP-2] × [IGFBP-7] for the development of AKI. RESULTS: Forty patients (mean age 55 ± 8 years) were included. Twenty-eight patients (70%) developed AKI stage 1, 2, or 3 within 48 h after OLT. Urinary [TIMP-2] × [IGFBP-7] was not predictive for AKI at the end of OLT (AUC: 0.54, CI [0.32-0.75], P = 0.72), at day 1 (AUC: 0.60, CI [0.41-0.79], P = 0.31), or day 2 after OLT (AUC: 0.63, CI [0.46-0.8], P = 0.18). CONCLUSION: Based on our results, routine clinical use of urinary [TIMP-2] × [IGFBP-7] cannot be recommended for risk assessment of AKI in patients undergoing OLT.

Patients Undergoing Orthotopic Liver Transplantation Require Lower Concentrations of the Volatile Anesthetic Sevoflurane.

BACKGROUND: Sevoflurane is a volatile anesthetic commonly used to maintain anesthesia in patients with end-stage liver disease (ESLD) undergoing orthotopic liver transplantation (OLT). Growing evidence suggests that patients with ESLD have decreased anesthetic requirements compared to patients with preserved liver function. The potency of volatile anesthetics is expressed as the minimum alveolar concentration (MAC). In this prospective, blinded study, we compared the MAC of sevoflurane among patients with ESLD undergoing OLT and patients with normal liver function undergoing major abdominal surgery. METHODS: After propofol-induced anesthesia, the MAC of sevoflurane was assessed by evaluating motor response to initial skin incision in patients undergoing OLT and in patients with normal liver function undergoing major abdominal surgery. The MAC was determined using Dixon "up-and-down" method and compared between groups. In addition, the bispectral index was documented immediately before and after skin incision. RESULTS: Twenty patients undergoing OLT and 20 control patients were included in the study. The MAC of sevoflurane in patients undergoing OLT was 1.3% (95% confidence interval [CI], 1.1-1.4). In comparison, the MAC of sevoflurane in patients with normal liver function was 1.7% (95% CI, 1.6-1.9), equal to a relative reduction of the MAC in patients with ESLD of 26% (95% CI, 14-39). The bispectral index was higher in patients with ESLD than in control patients at 3 minutes before (47 [95% CI, 40-53] vs 35 [95% CI, 31-40], P = .011), 1 minute before (48 [95% CI, 42-54] vs 37 [95% CI, 33-43], P = .03), and 1 minute after skin incision (57 [95% CI, 50-64] vs 41 [95% CI, 36-47], P < .001). CONCLUSIONS: Our results suggest that the MAC of sevoflurane is lower in patients with ESLD than in patients with normal liver function after propofol-induced anesthesia. However, as we did not measure propofol concentrations at the time of skin incision, the difference in MAC should be interpreted with caution given that residual propofol may have been present at the time of skin incision.

Graft-derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation.

Experimental studies suggest that macrophage migration inhibitory factor (MIF) mediates ischemia/reperfusion injury during liver transplantation. This study assessed whether human liver grafts release MIF during preservation, and whether the release of MIF is proportional to the extent of hepatocellular injury. Additionally, the association between MIF and early allograft dysfunction (EAD) after liver transplantation was evaluated. Concentrations of MIF, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured in effluents of 38 liver grafts, and in serum of recipients. Concentrations of MIF in the effluent were greater than those in the recipients' serum before and after reperfusion (58 [interquartile range, IQR:23-79] µg/mL vs 0.06 [IQR:0.03-0.07] µg/mL and 1.3 [IQR:0.7-1.8] µg/mL, respectively; both P<.001). Effluent MIF concentrations correlated with effluent concentrations of the cell injury markers ALT (R=.51, P<.01), AST (R=.51, P<.01), CK (R=.45, P=.01), and LDH (R=.56, P<.01). Patients who developed EAD had greater MIF concentrations in effluent and serum 10 minutes after reperfusion than patients without EAD (Effluent: 80 [IQR:63-118] µg/mL vs 36 [IQR:20-70] µg/mL, P=.02; Serum: 1.7 [IQR:1.2-2.5] µg/mL vs 1.1 [IQR:0.6-1.7] µg/mL, P<.001). CONCLUSION: Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.

The effect of a bolus dose of intravenous lidocaine on the minimum alveolar concentration of sevoflurane: a prospective, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: The anesthetic effect of volatile anesthetics can be quantified by the minimum alveolar concentration (MAC) of the drug that prevents movement in response to a noxious stimulus in 50% of patients. The underlying mechanism regarding how immobilization is achieved by volatile anesthetics is not thoroughly understood, but several drugs affect MAC. In this study, we investigated the effect of a single IV bolus dose of lidocaine on the MAC of sevoflurane in humans. METHODS: We determined the MAC for sevoflurane using the Dixon "up-and-down" method in 3 groups of patients, aged 30 to 65 years, who underwent elective surgery (30 patients per group). Study medication (placebo, 0.75 mg·kg(-1) lidocaine or 1.5 mg·kg(-1) lidocaine) was administered 3 minutes before skin incision after a 15-minute equilibration period and the response to skin incision was recorded (movement versus no movement). RESULTS: MAC was 1.86% ± 0.40% in the placebo and 1.87% ± 0.45% in the 0.75 mg·kg(-1) lidocaine group (P = 1.00). MAC was 1.63% ± 0.24% in the 1.5 mg·kg(-1) lidocaine group, which was significantly lower than that of the placebo group (mean difference of 0.23% sevoflurane [95% adjusted confidence interval {CI}, 0.03-0.43]; P = 0.022). No significant difference was observed between the 0.75 mg·kg(-1) lidocaine and the placebo groups (mean difference of -0.01% sevoflurane [95% adjusted CI, -0.27 to 0.25]; P = 1). CONCLUSIONS: IV 1.5 mg·kg(-1) lidocaine decreased the MAC by at least 0.03% sevoflurane (mean difference 0.23% sevoflurane [95% adjusted CI, 0.03-0.43]). We did not observe a significant reduction in the MAC of sevoflurane with the IV administration of 0.75 mg·kg(-1) lidocaine.

Medical information on the Internet: Quality assessment of lumbar puncture and neuroaxial block techniques on YouTube.

BACKGROUND: The Internet has become the largest, most up-to-date source for medical information. Besides enhancing patients' knowledge, the freely accessible audio-visual files have an impact on medical education. However little is known about their characteristics. In this manuscript the quality of lumbar puncture (LP) and spinal anaesthesia (SA) videos available on YouTube is assessed. METHODS: This retrospective analysis was based on a search for LP and SA on YouTube. Videos were evaluated using essential key points (5 in SA, 4 in LP) and 3 safety indicators. Furthermore, violation of sterile working techniques and a rating whether the video must be regarded as dangerously misleading was performed. RESULTS: From 2321 hits matching the keywords, 38 videos were eligible for evaluation. In LP videos, 14% contained information on all, 4.5% on 3 and 4.5% on 2 key points, 59% on 1 and 18% on no key point. Regarding SA, no video contained information on all 5 key points, 56% on 2-4 and 25% on 1 key point, 19% did not contain any essential information. A sterility violation occurred in 11%, and 13% were classified as dangerously misleading. CONCLUSIONS: Even though high quality videos are available, the quality of video clips is generally low. The fraction of videos that were not performed in an aseptic manner is low, but these pose a substantial risk to patients. Consequently, more high-quality, institutional medical learning videos must be made available in the light of the increased utilization on the Internet.

Perspectives for core and skin surface temperature guided extubation in patients after normothermic cardiopulmonary bypass.

OBJECTIVE: To investigate the relationship between changes in core and skin surface temperature and extubation time in patients following normothermic cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Patients admitted to the ICU after cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Thirty-two patients undergoing cardiac surgery with the use of normothermic CPB were studied. In the ICU, urinary bladder temperature and skin surface temperature gradient (forearm temperature minus fingertip temperature) were measured at 30-min intervals for 10 h postoperatively. Every half-hour an anaesthesiologist, blinded to temperature measurements, checked the possibility of extubation. On arrival in the ICU the mean skin surface temperature gradient of the patients was 1.9+/-1.6 degrees C, indicating vasoconstriction of the dermal vessels (>0 degrees C = vasoconstriction, <0 degrees C = vasodilation) while the mean urinary bladder temperature was 36.8+/-0.4 degrees C. The change from thermoregulatory vasoconstriction to vasodilation (skin surface temperature gradient of 0 degrees C) was 137+/-49 min after arrival in the ICU. The mean time until extubation was 135+/-55 min after arrival in the ICU. There was a linear relation between a temperature gradient of 0 degrees C and extubation time, r(2)=0.49. Later, 181+/-67 min after arrival in the ICU, the urinary bladder temperature reached its maximum of 38.2+/-0.6 degrees C. CONCLUSIONS: This study demonstrates that the transition period from peripheral vasoconstriction to vasodilation provides an opportunity for postoperative extubation.

Assessment of ventricular contractile function during orthotopic liver transplantation.

Hemodynamic alterations are a well-known phenomenon that influence the outcome of orthotopic liver transplantation (OLT). Whether or not myocardial dysfunction, which has various causes, contributes to this instability is still debated. Previous transesophageal echocardiography (TEE) studies have presented controversial data, not leading to final clarification. This is mainly because the impact of other contributing factors (inotropic support, alternating preload conditions and temperature) remained unaccounted for. We therefore measured the left ventricular shortening fraction (LVSF), a parameter reflecting myocardial contractility, in 10 consecutive patients undergoing OLT without veno-venous bypass. We measured during preparation (PP), during the anhepatic (AP) phase and the immediate reperfusion phase (RP). During the AP we observed a significant decrease of LVSF which never fell to subnormal levels in the majority of our patients, whereas during the RP, LVSF returned to PP values. These findings support the assumption that myocardial function is influenced by OLT, but that it plays only a minor role in the occurrence of hemodynamic instability, which could mainly be attributed to volume fluctuations.