Fibrinogen but not factor XIII deficiency is associated with bleeding after craniotomy.

BACKGROUND: Postoperative haemorrhage in neurosurgery is associated with significant morbidity and mortality. There is controversy whether or not factor XIII (FXIII) deficiency leads to bleeding complications after craniotomy. Decreased fibrinogen levels have been associated with an increased incidence of bleeding complications in cardiac and orthopaedic surgery. The aim of this study was to assess perioperative fibrinogen and FXIII levels in patients undergoing elective intracranial surgery with and without severe bleeding events. METHODS: Perioperative FXIII and fibrinogen levels were prospectively assessed in 290 patients undergoing elective craniotomy. Patients were divided into two groups according to the presence or absence of severe bleeding requiring surgical revision. Coagulation test results of these groups were compared using Student's t-test. RESULTS: The incidence of postoperative severe bleeding was 2.4%. No differences in FXIII levels were observed, but postoperative fibrinogen levels were significantly lower in patients suffering from postoperative haematoma compared with those without postoperative intracranial bleeding complications [237 mg dl(-1) (standard deviation, SD 86) vs 170 mg dl(-1) (SD 35), P=0.03]. The odds ratio for postoperative haematoma in patients with a postoperative fibrinogen level below 200 mg dl(-1) was 10.02 (confidence interval: 1.19-84.40, P=0.03). CONCLUSIONS: This study emphasizes the role of fibrinogen as potentially modifiable risk factor for perioperative bleeding in intracranial surgery. Future randomized controlled trials will be essential to identify patients who might benefit from fibrinogen substitution during neurosurgical procedures.

Austrian clinical practice with anidulafungin in 2008: a multicenter survey.

Anidulafungin had demonstrated favorable efficacy versus fluconazole in a randomized trial on invasive Candida infections. Since patient characteristics in the post-approval use of antifungals likely deviate from clinical trials, we surveyed the use of anidulafungin in clinical routine. We performed a retrospective survey of the post-approval use of anidulafungin in 9 Austrian clinical centers. Anidulafungin was used in 129 critically ill patients with severe comorbidities and multiple risk factors. Indications were suspected invasive fungal infections (IFI) (61%), proven candidemia (19%), and at risk for IFI (prophylaxis, 20%). Candida colonization in conjunction with other risk factors prompted treatment in many patients. predominant pathogens were C. albicans, C. glabrata and C. krusei. Anidulafungin was mostly used for pre-emptive (69%) and first-line treatment (17%) of invasive candidiasis. Treatment response, i.e. complete response/stabilization as determined by investigators (89% in the overall population; 87% for documented candidemia) and survival rates (81% and 75%, respectively) were similar to previous trial data. No breakthrough IFI and few adverse events were reported. Overall, favorable clinical experiences were documented with anidulafungin in the clinical routine setting.

Remifentanil for tracheal tube tolerance: a case control study.

We assessed the minimal remifentanil dosage required for tracheal tube tolerance in awake and spontaneously breathing patients after major abdominal surgery. Forty postoperative patients received remifentanil 0.1 microg.kg(-1).min(-1), which was reduced in steps of 0.025 microg.kg(-1).min(-1) every 30 min. Respiratory response subscore of comfort scale (CSRR), Ramsay sedation scale (RSS), visual analogue scale (VAS), respiratory rate, and minute ventilation were recorded. Spontaneous respiration with no or little response to ventilation (CSRR 2) in co-operative, oriented and tranquil patients (RSS 2) was defined as the main outcome and study endpoint. Thirty-one patients (77.5%) reached a CSRR 2 and RSS 2 with remifentanil 0.025 microg.kg(-1).min(-1) and nine patients (22.5%) required remifentanil 0.05 microg.kg(-1).min(-1). Analgesia was sufficient in all patients (VAS = 30). Remifentanil 0.025-0.05 microg.kg(-1).min(-1) achieves satisfactory tracheal tube tolerance in awake and spontaneously breathing patients.

The effect of skin surface warming on pre-operative anxiety in neurosurgery patients.

Skin surface warming of patients not only improves thermal comfort, but has been shown to reduce anxiety in a pre-hospital setting. We tested the hypothesis that pre-operative warming can reduce pre-operative anxiety as effectively as a conventional dose of intravenous midazolam in patients undergoing neurosurgery. We randomly allocated 80 patients to four groups in the pre-operative holding area. Treatment was applied for 30-45 min with (1) passive insulation and placebo; (2) passive insulation and intravenous midazolam (30 microg.kg-1); (3) warming with forced-air and placebo; and (4) warming with forced-air and intravenous midazolam (30 microg.kg-1). Thermal comfort levels (VAS 0-100 mm) and anxiety levels (VAS 0-100 mm, Spielberger State-Trait Anxiety Inventory) were assessed twice: before the designated treatment was started and before induction of anaesthesia. In the midazolam and the midazolam/warming groups, anxiety VAS and Spielberger state anxiety scores decreased by -19 (95% CI: -29 to -9, p<0.01) and -10 (95% CI: -14 to -6, p<0.01), respectively. In the warming and the combined groups, thermal VAS increased by +26 (95% CI: 17-34, p<0.01). Pre-operative warming did not reduce anxiety VAS (p=0.11) or Spielberger state anxiety (p=0.19). The results of our study indicate that pre-operative warming can be recommended solely to improve thermal comfort, not to replace anxiolytic premedication regimens.

Laparoscopic versus open myomectomy: a double-blind study to evaluate postoperative pain.

The advantages of laparoscopic over open surgery have been documented in nonblinded settings. Our prospective, double-blind setting evaluated pain scores 72 h after surgery by comparing patients who underwent laparoscopic myomectomy or with laparotomy. Forty women referred for conservative myomectomy were included in the study. After stratification (myoma size, number of myomas, and surgeon), patients were randomized to either laparoscopy (n = 19) or laparotomy (n = 21) and received a standardized anesthesia and patient-controlled analgesia for 24 h after surgery. Identical wound dressings were applied to blind the patient and the observer to the surgical approach. The postoperative pain scores were documented on a visual analog scale (VAS; 0 = no and 10 = unbearable pain) at 24, 48, and 72 h after surgery. As the primary outcome variable, we calculated the mean overall VAS-score at these time points. P < 0.05 (t-test and analysis of covariance) was considered statistically significant. There were no differences in patient characteristics among the groups. The mean overall VAS score at 24, 48, and 72 h was statistically significantly lower in the laparoscopic group compared with the laparotomy group (2.28 +/- 1.38 versus 4.03 +/- 1.63; P < 0.01). Our data demonstrate, for the first time in a double-blind setting, that laparoscopic myomectomy reduces postoperative pain for 72 h after surgery compared with laparotomy.

The effect of graded hypothermia (36 degrees C-32 degrees C) on hemostasis in anesthetized patients without surgical trauma.

UNLABELLED: The isolated effects of hypothermia on hemostasis have not been investigated in healthy humans. We cooled 16 anesthetized patients scheduled for elective intracranial surgery to 32 degrees C body core temperature and assessed prothrombin time (PT), activated partial thromboplastin time, thrombelastogram (TEG), closure time, and platelet count at 36 degrees C, 34 degrees C, and 32 degrees C body core temperature after the induction of anesthesia but before surgical intervention. Activated partial thromboplastin time, hematocrit, and closure time did not change, whereas PT and platelet count decreased during cooling. Platelet count decreased without a decrease in hematocrit; hence, a dilution by administered fluids seemed unlikely. The small decrease of platelet count is probably clinically irrelevant in patients with normal platelet count and function. The small decrease in PT indicates an alteration of the extrinsic pathway of coagulation. TEG measurements showed a delay of clot formation in temperature-adjusted measurements but showed no change if the test temperature was 37 degrees C. This indicates that hypothermia reduces plasmatic coagulation and platelet reactivity. However, the clot strength is not altered by hypothermia. All coagulation variables remained within the normal ranges. Our results may indicate that moderate short-term (4-h) hypothermia has only minor adverse effects in healthy humans. We can make no statement about the effects of hypothermia of longer duration. IMPLICATIONS: This study investigated the isolated effects of hypothermia in healthy anesthetized humans. We found only minor effects of body temperature reduction to 32 degrees C on assessed coagulation variables, indicating only minor effects in otherwise healthy humans.

A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity.

We compared systemic (aortic) blood flow and cerebral blood flow velocity in 30 patients randomly allocated to receive either propofol or sevoflurane anaesthesia. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery using transcranial Doppler. Systemic blood flow velocity (SBFv) was measured in the aorta using transthoracic Doppler sonography at the level of the aortic valve. Bispectral index (BIS) was used to measure the depth of anaesthesia. Measurements were made in the awake patient and repeated during propofol or sevoflurane anaesthesia, with BIS measurements of 40-50. The effects of SBFv on CBFv were estimated by calculating the cerebral/systemic blood flow velocity-index (CsvI). A CsvI value of 100 indicating a 1 : 1 relationship between CBFv and SBFv. The results demonstrated that propofol anaesthesia produced a significantly greater reduction in CsvI than did sevoflurane anaesthesia [propofol: 60 (19); sevoflurane: 83 (16), p = 0.009, t-test]. This suggests a direct reduction in CBFv independent of SBFv during propofol anaesthesia. The greater reduction of CBFv occurring during propofol anaesthesia may be due to lower cerebral metabolic demand compared with sevoflurane anaesthesia at comparable depths of anaesthesia.

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.

Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To analyze the influence of extracerebral organ system dysfunction after aneurysmal subarachnoid hemorrhage (SAH) on mortality and neurologic outcome. DESIGN: Observational study with retrospective data extraction. SETTING: Neurosurgical intensive care unit (NICU) at a primary level university hospital, supervised and staffed by both members of the Clinic of Neurosurgery and the Clinic of Anesthesiology and General Intensive Care. PATIENTS: Two hundred forty-two patients treated for intracranial aneurysm rupture within 7 days of the most recent SAH. INTERVENTIONS: Routine neurosurgical interventions for obliteration of the ruptured aneurysm (microsurgery, Guglielmi Detachable Coils embolization) and for treatment of posthemorrhagic hydrocephalus (ventriculostomy, cerebrospinal fluid shunt implantation). MEASUREMENTS AND MAIN RESULTS: Respiratory, renal, hepatic, cardiovascular, and hematologic organ system functions were evaluated both individually and in aggregate by using a modified version of the Multiple Organ Dysfunction (mMOD) score. Of 1,452 organ system functions assessed in 242 patients during their NICU stay, 714 organ system functions were intact (cerebral: 0, extracerebral: 714), 556 organ systems had mild-to-moderate dysfunctions (mMOD scoremax 1-2 for the affected organ system; cerebral: 153, extracerebral: 403), and 182 organ systems failed (mMOD scoremax 3 for the affected organ system; cerebral: 89, extracerebral: 93). Severity of extracerebral organ system dysfunctions correlated with the degree of neurologic impairment (Hunt and Hess [H&H] score) in a graded fashion. Similarly, the chance to develop systemic inflammatory response syndrome (SIRS) during the NICU stay increased with increasing admission H&H grade. The incidence of SIRS and septic shock was 29% and 10.3%, respectively. The mortality rate was 40.2% in patients with SIRS and 80% for patients suffering septic shock. Seventy-seven percent of extracerebral organ system failures (OSFs) occurred in conjunction with SIRS: 51% of respiratory OSFs, 97% of renal OSFs, 100% of hepatic OSFs, 96% of cardiovascular OSFs, and 73% of hematopoietic OSFs. Both CNS dysfunction and extracerebral organ system dysfunctions were significantly related to neurologic outcome. The probability of unfavorable neurologic outcome significantly increased with both decreasing cerebral perfusion pressure (CPP) and increasing severity of extracerebral organ dysfunction. CONCLUSION: Aneurysmal SAH and its neurologic sequelae accounted for the principal morbidity and mortality in the current series. Development of extracerebral organ system dysfunction was associated with a higher probability of unfavorable neurologic outcome. Systemic inflammation (SIRS) and secondary organ dysfunction were the principal non-neurologic causes of death.

The arterial to end-tidal carbon dioxide gradient increases with uncorrected but not with temperature-corrected PaCO2 determination during mild to moderate hypothermia.

UNLABELLED: End-tidal carbon dioxide (PETCO2) monitoring is recommended as a basic standard of care and is helpful in adjusting mechanical ventilation. Gas solubility changes with temperature, which might affect the PaCO2 and thereby the gradient between PaCO2 and PETCO2 (PA-ETCO2) under hypothermic conditions. We investigated whether the PA-ETCO2 changes during mild to moderate hypothermia (36 degrees C-32 degrees C) using PaCO2 measured at 37 degrees C (uncorrected PaCO2) and PaCO2 corrected to actual body temperature. We preoperatively investigated 19 patients. After anesthesia had been induced, controlled ventilation was established to maintain normocarbia using constant uncorrected PaCO2 to adjust ventilation (alpha-stat acid-base regimen). Body core temperature was reduced without surgical intervention to 32 degrees C by surface cooling. Continuous PETCO2 was monitored with a mainstream PETCO2 module. The PA-ETCO2 was calculated using the uncorrected and corrected PaCO2 values. During body temperature reduction from 36 degrees C to 32 degrees C, the gradient between PETCO2 and uncorrected PaCO2 increased 2.5-fold, from 4.1 +/- 3.7 to 10.4 +/- 3.8 mm Hg (P < 0.002). The PA-ETCO2 remained unchanged when the corrected PaCO2 was used for the calculation. We conclude that when the alpha-stat acid-base regimen is used to adjust ventilation, the PA-ETCO2 calculated with the uncorrected PaCO2 increases and should be added to the differential diagnosis of widened PA-ETCO2. In contrast, when the corrected PaCO2 is used for the calculation of the PA-ETCO2, the PA-ETCO2 remains unaltered during hypothermia. IMPLICATIONS: We investigated the impact of induced hypothermia (36 degrees C-32 degrees C) on the gradient between PaCO2 and PETCO2 (PA-ETCO2). The PA-ETCO2 increased 2.5-fold when CO2 determinations were not temperature-corrected. Hypothermia should be added to the differential diagnosis of an increased PA-ETCO2 when the alpha-stat acid-base regimen is used.

The cerebral and cardiovascular effects of cisatracurium and atracurium in neurosurgical patients.

UNLABELLED: Drugs for neurosurgical patients should not increase intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow. This double-blind, cross-over study compares the effects of a single (3 x effective dose producing 95% twitch depression) intravenous bolus dose of cisatracurium 0.15 mg/kg with atracurium 0.75 mg/kg on mean red blood cell flow velocity in the middle cerebral artery (CBFV; transcranial Doppler), ICP (intraventricular or intraparenchymal monitor), mean arterial pressure (MAP), CPP (MAP-ICP), and heart rate (HR) every minute during a 15-min study period. Included in the study were 14 sedated and ventilated adult neurosurgical patients. After the cisatracurium bolus, ICP, CPP, CBFV, MAP, and HR did not change, and no histamine related events were observed. After the atracurium bolus, ICP, CPP, CBFV, and MAP decreased. The lowest values of ICP (-16% of baseline), CPP (-5%), CBFV (-8%), and MAP (-7%) were recorded 2-4 min after the atracurium bolus injection. After this transient decrease, MAP and CPP returned to baseline, whereas CBFV and ICP transiently exceeded baseline values. The highest values of CBFV (5%) and ICP (17%) were recorded 9-12 min after the atracurium bolus injection. Five patients showed a typical histamine response after atracurium, with a decrease in MAP and flushing. Excluding these five patients eliminated statistical significance in ICP, CPP, CBFV, and MAP differences. In conclusion, cisatracurium demonstrated fewer cerebral and cardiovascular hemodynamic side effects in sedated adult neurosurgical patients. IMPLICATIONS: This double-blind study in sedated and mechanically ventilated adult neurosurgical patients demonstrates that an intravenous bolus dose of the neuromuscular blocker cisatracurium results in less cerebral (intracranial pressure, cerebral perfusion pressure, middle cerebral artery blood flow velocity) and cardiovascular (blood pressure) hemodynamic side effects, compared with an equipotent dose of atracurium.

Pulmonary function and radiographic abnormalities related to neurological outcome after aneurysmal subarachnoid hemorrhage.

OBJECT: This observational study is based on a consecutive series of 207 patients with aneurysmal subarachnoid hemorrhage who were treated within 7 days of their most recent bleed. The purpose of the study was to evaluate the effect of respiratory failure on neurological outcome. METHODS: Pulmonary function was assessed by determination of parameters describing pulmonary oxygen transport and exchange, by using composite scores for quantification of lung injury (lung injury score [LIS]) and mechanical ventilator settings (PIF score). Pulmonary function was related to the Hunt and Hess (H & H) grade assigned to the patient at hospital admission (p < 0.001). The pattern and time course of lung injury differed significantly between patients with H & H Grade I or II, Grade III, and Grade IV or V. Hunt and Hess grade, Fisher computerized tomography grade, intracranial pressure, cerebral perfusion pressure, LIS, ratio of PaO2 to the fraction of inspired oxygen (FiO2), and the ratio of the alveolar-minus-arterial oxygen tension difference (AaDO2) to FiO2 were related to neurological outcome (p < 0.001). The LIS on the day of maximum lung injury remained an independent predictor of outcome (p = 0.01) in a stepwise logistic regression analysis. The probability of poor neurological outcome significantly increased with both decreasing cerebral perfusion pressure and increasing severity of lung injury. CONCLUSIONS: The overall mortality rate was 22.2% (46 of 207 patients). Subarachnoid hemorrhage and its neurological sequelae accounted for the principal mortality in this series. Medical (nonneurological and nontreatment-related) complications accounted for 37% of all deaths. Systemic inflammatory response syndrome with associated multiple organ dysfunction syndrome was the leading cause of death from medical complications. The authors conclude that respiratory failure is related to neurological outcome, although it is not commonly the primary cause of death from medical complications.

Changes in oxygenation variables during progressive hypothermia in anesthetized patients.

Because deliberate hypothermia is becoming commonly used during neurosurgery, this study was performed to investigate the effects of a progressive reduction of body core temperature (T) on whole body oxygenation variables in patients undergoing elective intracranial surgery. In 13 patients (Hypothermic Group), T was reduced to 32.0 degrees C using convective-based surface cooling. In six patients (Control Group), T was maintained at 35.5 degrees C during the entire study period. The cardiac index (CI) was determined with a pulmonary artery catheter by thermodilution. Whole body oxygen delivery (DO2) was calculated from CI and arterial oxygen content. Whole body oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (EE) were determined by ventilation gas analysis (indirect calorimetry). Mixed venous oxygen tension at 50% saturated hemoglobin (P50), and whole body oxygen extraction ratio (O2ER) were calculated. Repeated-measures analysis of variance and the Mann-Whitney test were used for statistical analysis. Data are expressed as means +/- SD. VO2 (from 100 +/- 13 to 77 +/- 11 ml.min-1.m-2), VCO2 (from 75 +/- 7 to 57 +/- 7 ml.min-1. m-2), EE (from 667 +/- 67 to 509 +/- 66 kcal.d-1.m-2), P50 (from 23.8 +/- 1.7 to 20 +/- 0.9 mm Hg), and O2ER (from 0.29 +/- 0.05 to 0.22 +/- 0.03%) decreased significantly in the Hypothermic Group between 35.5 and 32.0 degrees C (p < 0.05). None of these variables changed in the Control Group and at 32.0 degrees C VO2, VCO2, EE, P50, and O2ER were significantly lower in the Hypothermic Group than in the Control Group. DO2 remained unchanged in both groups. We conclude that progressive hypothermia in anesthetized patients reduces metabolic rate but does not change DO2. The significant decrease in O2ER may partly be related to a leftward shift of the oxyhemoglobin dissociation curve, as evidenced by the decrease in P50.