Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity.

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8+ T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously1. Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter2,3, but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively4,5. Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands6-8. TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP-PKA-CREB axis for enhanced CD8+ T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8+ T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours.

Continuous bupivacaine infusion post-iliac crest bone graft harvesting in pediatric cleft surgery: role and comparison with ketorolac.

OBJECTIVE: To investigate the use of intravenous ketorolac and iliac crest bupivacaine infusion in the management of iliac crest donor-site pain in the pediatric cleft population. The null hypothesis was there is no difference with respect to pain scores between ketorolac and iliac crest bupivacaine infusion as analgesic adjuncts to intravenous opioids. METHODS: A total of 54 children and adolescents (27 boys, 27 girls) undergoing alveolar cleft repair or Le Fort I osteotomy were assigned randomly in a prospective, single-blinded fashion to one of three groups: intravenous ketorolac plus iliac crest normal saline infusion, intravenous ketorolac plus iliac crest bupivacaine infusion, or iliac crest bupivacaine infusion alone. Iliac crest infusions and ketorolac were administered for 48 hours or until discharge, whichever occurred first. All patients received morphine via a patient-controlled analgesia device. MAIN OUTCOME MEASURE(S): Primary outcome was pain score, and secondary outcomes were morphine consumption and satisfaction scores. RESULTS: Pain scores, morphine consumption, and satisfaction scores were not significantly different among groups. Estimated costs were significantly higher for bupivacaine infusion than intravenous ketorolac. CONCLUSIONS: Iliac crest donor-site pain is well managed in this patient population. Intravenous ketorolac and iliac crest bupivacaine infusion provide comparable analgesia for iliac crest bone graft donor-site pain in children and adolescents.

The effect of sevoflurane on cerebral blood flow velocity in children.

BACKGROUND: Sevoflurane is a suitable agent for neuroanesthesia in adult patients. In children, cerebrovascular carbon dioxide reactivity is maintained during hypo- and normocapnia under sevoflurane anesthesia. To determine the effects of sevoflurane on middle cerebral artery blood flow velocity (Vmca) in neurologically normal children, Vmca was measured both at different MAC values and at one MAC over a specified time period, using transcranial Doppler sonography. METHODS: Twenty-six healthy children undergoing elective urological surgery were enrolled (16 patients in part I and 10 in part II). In part I of the study anesthesia comprised sevoflurane 0.5, 1.0 and 1.5 MAC in 30% oxygen and a caudal epidural block. Once steady state had been reached at each sevoflurane MAC level, three measurements of Vmca, mean arterial pressure (MAP) and heart rate (HR) were recorded. In part II of the study patients received sevoflurane 1.0 MAC over a 90-min period, with the same variables being recorded at 15-min intervals. RESULTS: Vmca did not vary significantly at 0.5, 1.0 and 1.5 MAC sevoflurane. There was a significant decrease in MAP between 0.5 MAC and 1.0 MAC sevoflurane (P < 0.005) and also between 1.0 MAC and 1.5 MAC (P < 0.01). There was no significant change in Vmca over 90 min at 1.0 MAC sevoflurane. CONCLUSION: Sevoflurane does not significantly affect cerebral blood flow velocity in healthy children at working concentrations.

The effect of nitrous oxide on cerebrovascular reactivity to carbon dioxide in children during propofol anesthesia.

Nitrous oxide (N(2)O) increases cerebral blood flow when used alone and in combination with propofol. We investigated the effects of N(2)O on cerebrovascular CO(2) reactivity (CCO(2)R) during propofol anesthesia in 10 healthy children undergoing elective urological surgery. Anesthesia consisted of a steady-state propofol infusion and a continuous caudal epidural block. A transcranial Doppler probe was used to measure middle cerebral artery blood flow velocity. Randomization determined the sequence order of N(2)O (N(2)O/air or air/N(2)O) and end-tidal (ET)CO(2) concentration (25, 35, 45, and 55 mm Hg) using an exogenous source of CO(2). At steady state, three sets of measurements of middle cerebral artery blood flow velocity, mean arterial blood pressure, and heart rate were recorded. A linear preservation of CCO(2)R was observed above 35 mm Hg of ETCO(2), irrespective of N(2)O. A decrease in CCO(2)R to 1.4%-1.9% per millimeters of mercury was seen in the hypocapnic range (ETCO(2) 25-35 mm Hg) with both air and N(2)O. We conclude that N(2)O does not affect CCO(2)R during propofol anesthesia in children. When preservation of CCO(2)R is required, the combination of N(2)O with propofol anesthesia in children would seem suitable. The cerebral vasoconstriction caused by propofol would imply that hyperventilation to ETCO(2) values less than 35 mm Hg may not be required because no further reduction in cerebral blood flow velocity would be achieved.

The effect of nitrous oxide on cerebral blood flow velocity in children anesthetized with propofol.

BACKGROUND: Propofol for maintenance of anesthesia by continuous infusion is gaining popularity for use in pediatric patients. Nitrous oxide (N2O) has been shown to increase cerebral blood flow velocity (CBFV) in both children and adults. To determine the effects of N2O on middle cerebral artery blood flow velocity (Vmca) during propofol anesthesia in children, Vmca was measured with and without N2O using transcranial Doppler (TCD) sonography. METHODS: Thirty ASA I or II children aged 18 months to 6 years undergoing elective urological surgery were enrolled. Anesthesia comprised propofol aimed at producing an estimated steady-state serum concentration of 3 micro g.ml-1 and a caudal epidural block. A transcranial Doppler probe was used to measure middle cerebral artery blood flow velocity. Each patient was randomized to receive a sequence of either Air/N2O/Air or N2O/Air/N2O in 35% oxygen. Fifteen min after each change in the N2O concentration, three measurements of cerebral blood flow velocity, blood pressure and heart rate were recorded. Ventilatory parameters and EtCO2 were kept constant throughout the study period. RESULTS: CBFV increased by 12.4% when air was replaced by N2O, and returned to baseline when N2O was subsequently removed. There was a 14% decrease in CBFV when N2O was replaced with air, which increased to baseline when air was subsequently replaced with N2O. Mean heart rate and blood pressure remained constant throughout the study period. CONCLUSION: The effects of nitrous oxide on CBFV are preserved in children during propofol anesthesia.

The effect of nitrous oxide on cerebral blood flow velocity in children anaesthetised with desflurane.

The aim of this study was to determine the effect of nitrous oxide on cerebral blood flow velocity in children anaesthetised with desflurane. Eighteen healthy children scheduled for elective surgery were enrolled into the study. Anaesthesia was induced using sevoflurane, and a caudal block was performed following tracheal intubation. Anaesthesia was maintained with 1 age-adjusted MAC desflurane. A transcranial Doppler probe was used to measure middle cerebral artery blood flow velocity. Each patient was randomised to receive a sequence of either air/nitrous oxide/air or nitrous oxide/air/nitrous oxide in 30% oxygen. Fifteen minutes after each change in the nitrous oxide concentration, three measurements of cerebral blood flow velocity, blood pressure and heart rate were recorded. Neither the addition nor removal of nitrous oxide caused any significant changes in middle cerebral artery blood flow velocity, heart rate or blood pressure. This may be due to a more potent cerebral vasodilatory effect of desflurane in children.

Cerebrovascular carbon dioxide reactivity in children anaesthetized with sevoflurane.

BACKGROUND: To determine the effects of sevoflurane on cerebrovascular carbon dioxide reactivity (CCO2R), middle cerebral artery blood flow velocity (CBFV) was measured at different levels of PE'CO2 by transcranial Doppler sonography in 16 ASA I or II children, aged 18 months to 7 yr undergoing elective urological surgery. METHODS: Anaesthesia comprised 1.0 MAC sevoflurane and air in 30% oxygen delivered through an Ayre's T piece by intermittent positive-pressure ventilation, and a caudal epidural block with 0.25% bupivacaine 1.0 ml kg(-1) without epinephrine. PE'CO2 was randomly adjusted to 25, 35, 45 and 55 mm Hg (3.3, 4.6, 5.9 and 7.2 kPa) with an exogenous source of CO2, while maintaining ventilation variables constant. RESULTS: CBFV increased as PE'CO2 increased from 25 to 35, and to 45 mm Hg (P<0.001), but did not increase significantly with an increase in PE'CO2 from 45 to 55 mm Hg. Mean heart rate and arterial pressure remained constant. CONCLUSION: CCO2R is preserved in healthy children anaesthetized with 1.0 MAC sevoflurane.

Effect of halothane on the cerebral circulation in young children: a hysteresis phenomenon.

To determine the effect of halothane on the cerebral blood flow velocity (CBFV) with increasing then decreasing concentrations, 11 children scheduled for minor surgery were studied. Anaesthesia consisted of halothane, vecuronium, nitrous oxide in oxygen and a caudal block. End-tidal carbon dioxide, temperature, heart rate and systolic arterial pressure were maintained constant. CBFV increased significantly between 0.5 and 1.0 MAC (p <0.001), and 0.5 and 1.5 MAC of halothane (p <0.001), but was not different after increasing concentration from 1.0 to 1.5 MAC. During the decreasing phase, CBFV decreased significantly from 1.5 to 1.0 MAC of halothane (p <0.001), whereas there was no difference in CBFV when decreasing halothane MAC from 1.0 to 0.5 MAC. In children, the decrease in CBFV during decreasing halothane concentration is not superimposable to the increase in CBFV seen when increasing halothane concentration, suggesting the presence of cerebrovascular hysteresis to halothane.

Human errors in a multidisciplinary intensive care unit: a 1-year prospective study.

OBJECTIVES: To determine the incidence and identify risk factors of critical incidents in an ICU. DESIGN: Prospective observational study of consecutive patients admitted over 1 year to an ICU. Critical incidents were recorded using predefined criteria. Their causes and consequences were analysed. The causes were classified as technical failure, patient's underlying disease, or human errors (subclassified as planning, execution, or surveillance). The consequences were classified as lethal, leading to sequelae, prolonging the ICU stay, minor, or without consequences. The correlation between critical incidents and specific factors including patient's diagnosis and severity score, use of monitoring and therapeutic modalities was analysed by uni- and multivariate analysis. SETTING: An 11-bed multidisciplinary ICU in a non-university teaching hospital. PATIENTS: 1,024 consecutive patients admitted to the ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The median length of ICU stay by the 1,024 patients was 1.9 days. Of the 777 critical incidents reported 2% were due to technical failure and 67 % to secondary to underlying disease. There were 241 human errors (31%) in 161 patients, evenly distributed among planning (n = 75), execution (n = 88), and surveillance (n = 78). One error was lethal, two led to sequelae, 26 % prolonged ICU stay, and 57 % were minor and 16 % without consequence. Errors with significant consequences were related mainly to planning. Human errors prolonged ICU stay by 425 patient-days, amounting to 15 % of ICU time. Readmitted patients had more frequent and more severe critical incidents than primarily admitted patients. CONCLUSIONS: Critical incidents add morbidity, workload, and financial burden. A substantial proportion of them are related to human factors with dire consequences. Efforts must focus on timely, appropriate care to avoid planning and execution mishaps at the beginning of the ICU stay; surveillance intensity must be maintained, specially after the fourth day.

The effect of low concentrations of halothane on the cerebrovascular circulation in young children.

To determine the effect of halothane on cerebral blood flow velocity measured by transcranial Doppler, 23 healthy young children were studied during surgery. Anaesthesia was induced with thiopental, fentanyl and vecuronium, and maintained with halothane in 70% nitrous oxide in oxygen. A continuous epidural anaesthesia with 0. 25% bupivacaine was performed. End-tidal carbon dioxide pressure, temperature, heart rate and systolic blood pressure were kept constant. Three minimal alveolar concentrations (MAC; 0.5, 1.0 and 1. 5) of halothane were administered in stepwise increases. The cerebral blood flow velocity increased significantly at 1.0 (p < 0. 01) and 1.5 MAC (p < 0.001) compared with the value at 0.5 MAC. No further change in cerebral blood flow velocity was seen between 1.0 and 1.5 MAC. These data show that maximal changes in cerebral blood flow velocity are obtained at 1.0 MAC and that further increases in halothane concentration do not modify the cerebral circulation. It is suggested that young children differ from adults in that the maximal effect of halothane occurs at lower concentrations.

Effects of neck position and head elevation on intracranial pressure in anaesthetized neurosurgical patients: preliminary results.

This study reports the collective effect of the positions of the operating table, head, and neck on intracranial pressure (ICP) of 15 adult patients scheduled for elective intracerebral surgery. Patients were anesthetized with propofol, fentanyl, and maintained with a propofol infusion and fentanyl. Intracranial pressure was recorded following 20 minutes of stabilization after induction at different table positions (neutral, 30 degrees head up, 30 degrees head down) with the patient's neck either 1) straight in the axis of the body, 2) flexed, or 3) extended, and in the five following head positions: a) head straight, b) head angled at 45 degrees to the right, c) head angled at 45 degrees to the left, d) head rotated to the right, or e) head rotated the left. For ethical reasons, only patients with ICP < or = 20 mm Hg were included. Intracranial pressure increased every time the head was in a nonneutral position. The most important and statistically significant increases in ICP were recorded when the table was in a 30 degree Trendelenburg position with the head straight or rotated to the right or left, or every time the head was flexed and rotated to the right or left-whatever the position of the table was. These observations suggest that patients with known compromised cerebral compliance would benefit from monitoring ICP during positioning, if the use of a lumbar drainage is planed to improve venous return, cerebral blood volume, ICP, and overall operating conditions.

Deep hypothermia and rewarming alters glutamate levels and glycogen content in cultured astrocytes.

BACKGROUND: Deep hypothermia has been associated with an increased incidence of postoperative neurologic dysfunction after cardiac surgery in children. Recent studies suggest an excitotoxic mechanism involving overstimulation of glutamate receptors. Extracellular glutamate uptake occurs primarily by astrocytes. Astrocytes also store glycogen, which may be used to sustain the energy-consuming glutamate uptake. Extracellular glutamate and glycogen content were studied during temperature changes mimicking cardiopulmonary bypass in vivo. METHODS: Primary cultures of cerebral cortical astrocytes were used in a specially designed incubator allowing continuous changes of temperature and ambient gas concentrations. The sequence of events was as follows: normothermia, rapid cooling (2.8 degrees C/min) followed by 60 min of deep hypothermia (15 degrees C), followed by rewarming (3.0 degrees C/min) and subsequent 5 h of mild hyperthermia (38.5 degrees C). Two different conditions of oxygenation were studied: (1) normoxia (25% O2, 70% N2, 5% CO2); or (2) hyperoxia (95% O2, 5% CO2). The extracellular glutamate concentrations and intracellular glycogen levels were measured at nine time points. RESULTS: One hundred sixty-two cultures were studied in four independent experiments. The extracellular concentration of glutamate in the normoxic group increased significantly from 35+/-10 nM/mg protein at baseline up to 100+/-15 nM/mg protein at the end of 5 h of mild hyperthermia (P < 0.05). In contrast, extracellular glutamate levels did not vary from control in the hyperoxic group. Glycogen levels decreased significantly from 260+/-85 nM/mg protein at baseline to < 25+/-5 nM/mg protein at the end of 5 h in the normoxic group (P < 0.05) but returned to control levels after rewarming in the hyperoxic group. No morphologic changes were observed in either group. CONCLUSION: The extracellular concentration of glutamate increases, whereas the intracellular glycogen content decreases when astrocytes are exposed to a sequence of deep hypothermia and rewarming. This effect of hypothermia is prevented when astrocytes are exposed to hyperoxic conditions.

Thermal regulation and mild intraoperative hypothermia.

Homeothermic species such as birds and mammals require an almost constant internal body temperature to preserve normal physiological and metabolic function. When the internal temperature deviates significantly from normal, metabolic function deteriorates and death may result. The efficiency of the thermoregulatory system is highly affected by the administration of medication and by illnesses. Hypothermia may result, especially when these conditions are associated with exposure to a cold environment. Because such conditions exist during anaesthesia and surgery, the understanding of the physiology of the thermoregulatory system and the associated perianaesthetic thermal disturbances is essential to a proper intraoperative management. The purpose of this review is to provide clinicians with a better understanding of these principles, and also to elaborate on the most recent advances in this field, which should help to improve intraoperative anaesthetic temperature management.

Cerebral physiology in paediatric cardiopulmonary bypass.

PURPOSE: To analyze studies of neurological injury after open-heart surgery in infants and children and to discuss the effects of cardiopulmonary bypass, hypothermia and deep hypothermic circulatory arrest on cerebral blood flow, cerebral metabolism and brain temperature. SOURCE: Articles were obtained from the databases, Current Science and Medline, from 1966 to present. Search terms include cardiopulmonary bypass (CPB), hypothermia, cerebral blood flow (CBF), cerebral metabolism and brain temperature. Information and abstracts obtained from meetings on the topic of brain and cardiac surgery helped complete the collection of information. PRINCIPAL FINDINGS: In adults the incidence of neurological morbidity is between 7 to 87% with stroke in about 2-5%, whereas the incidence of neurological morbidity increases to 30% in infants and children undergoing cardiopulmonary bypass. Besides the medical condition of the patient, postoperative cerebral dysfunction and neuronal ischaemia associated with cardiac surgery in infants and small children are a combination of intraoperative factors. Deep hypothermic circulatory arrest impairs CBF and cerebral metabolism even after termination of CPB. Inadequate and/or non-homogenous cooling of the brain before circulatory arrest, as well as excessive rewarming of the brain during reperfusion are also major contributory factors. CONCLUSION: Newer strategies, including the use of low-flow CPB, pulsatile CPB, pH-stat acid-base management and a cold reperfusion, are being explored to ensure better cerebral protection. Advances in monitoring technology and better understanding of the relationship of cerebral blood flow and metabolism during the different modalities of cardiopulmonary bypass management will help in the medical and anaesthetic development of strategies to improve neurological and developmental outcomes.

-The effect of ondansetron on intracranial pressure and cerebral perfusion pressure in neurosurgical patients-. / Effet de l'ondansétron sur la pression intracrânienne et la pression de perfusion cérébrale chez le patient neurochirurgical.

OBJECTIVE: To determine the effect of ondansetron on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP). STUDY DESIGN: Prospective, comparative, randomized double-blind study. PATIENTS: Twenty-six patients undergoing intracranial surgery. METHOD: Induction was obtained with propofol (1-2.5 mg.kg-1), fentanyl (1.5 micrograms.kg-1) and pancuronium (0.1 mg.kg-1), and maintenance was achieved with propofol and fentanyl. Intermittent positive pressure ventilation was used to ensure mild hypocapnia at 35 +/- 2 mmHg. Positioning of the patient was followed by 15 minutes steady-state. Patient received thereafter either 8 mg ondansetron or a placebo intravenously. The ICP was measured using a lumbar malleable spinal needle. CPP was calculated using the formula CCP = MAP-ICP. All variables were measured every minute for 15 minutes. RESULTS: The ICP, MAP and CPP did not differ between the two groups. There were no differences in the highest ICP values in patients receiving either ondansetron or placebo (11 +/- 5 versus 9 +/- 5, mean +/- SD), respectively. CONCLUSION: Intravenous administration of 8 mg ondansetron affects neither cerebral hemodynamics nor ICP.

Bupivacaine 0.125% produces motor block and weakness with fentanyl epidural analgesia in children.

PURPOSE: Epidural infusions of fentanyl (2 micrograms.ml-1) alone or combined with bupivacaine 0.125% were compared for perioperative analgesia, motor block and other side-effects in children who underwent urological surgery. METHODS: In a prospective, double-blind study, 42 children, ASA I-II, 1-16 yr, were randomly allocated to receive either epidural F (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 saline followed by 2 micrograms.ml-1 fentanyl infusion) or epidural F-B (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 bupivacaine 0.25% followed by 2 micrograms.ml-1 fentanyl infusion in bupivacaine 0.125%) after induction of general anaesthesia. Adequacy of analgesia, lower limb motor block and side-effects were assessed four hourly postoperatively. RESULTS: Both infusion regimens provided excellent analgesia (median objective pain scores = 0). Epidural infusion rates were similar in the F (0.29 +/- 0.07 ml.kg-1.hr-1) and F-B (0.26 +/- 0.05 ml.kg-1.hr-1) groups. Three children in the F group and all children in the F-B group developed lower limb weakness. (P < 0.05) Bromage scores were different in the F group (median 0, range 0-0.66) compared with the F-B group (median 0.33, range 0-1) (P < 0.001). Other side-effects did not differ. CONCLUSION: Postoperative epidural fentanyl infusion provides equipotent analgesia to administration of a solution including both fentanyl and bupivacaine 0.125% and causes less lower limb weakness. No reduction in the fentanyl requirement resulted from the addition of bupivacaine 0.125%.

Enflurane decreases the threshold for vasoconstriction more than isoflurane or halothane.

Intraoperative hypothermia results largely from anesthetic-induced inhibition of tonic thermoregulatory vasoconstriction. Sufficient hypothermia, however, triggers peripheral vasoconstriction, which usually prevents further decrease in core temperature. The thermoregulatory effects of all volatile anesthetics have been tested in adults and/or children, but different anesthetics have not been directly compared. We therefore evaluated thermoregulatory responses during enflurane, isoflurane, and halothane administration. Anesthesia was maintained with 1 minimum alveolar anesthetic concentration (MAC) of halothane, isoflurane, or enflurane in 27 patients undergoing intraabdominal surgery. Patients were maintained normovolemic and normocapnic but were allowed to cool passively. A forearm minus fingertip, skin-temperature gradient of 4 degrees C identified significant vasoconstriction; the core temperature triggering vasoconstriction identified the threshold. Morphometric characteristics, initial core temperatures, ambient operating room temperatures, blood pressures, and anesthetic potencies were similar in each group. All eight patients given halothane vasoconstricted at a core temperature of 35.5 +/- 0.6 degrees C. Eight of the patients given isoflurane vasoconstricted at a core temperature of 35.2 +/- 0.5 degrees C. However, two others did not at minimum core temperatures of 34.0 and 33.8 degrees C. Only one patient given enflurane vasoconstricted at a core temperature of 34.6 degrees C. The other six patients never vasoconstricted, at minimum core temperatures of 33.6 +/- 0.4 degrees C. Our data indicate that enflurane profoundly inhibits thermoregulatory responses in children. The mechanism for this extraordinary inhibition remains unknown but does not result from any obvious anesthetic pharmacology or thermoregulatory physiology. We conclude that unwarmed pediatric patients will become colder when anesthetized with enflurane than with halothane or isoflurane.

Dimenhydrinate decreases vomiting after strabismus surgery in children.

Dimenhydrinate, an H1-receptor antagonist, has been used to both prevent and treat postoperative vomiting (POV) in children for several decades. However, its effectiveness for POV after strabismus surgery remains anecdotal. This study was designed to determine the effectiveness and side effects of dimenhydrinate for the prevention of POV in children after strabismus surgery. Eighty ASA physical status I or II children, ages 1-12 yr inclusive, who were undergoing strabismus surgery, were prospectively and randomly allocated to receive either dimenhydrinate 0.5 mg/kg intravenously (n = 40) or placebo (n = 40) at induction of anesthesia. The incidence of POV and the times to arousal (and discharge from the recovery room and hospital) were recorded postoperatively in a double blinded manner. For 24 h after discharge from the hospital, all emetic episodes and medications given were recorded by the parents. Demographic data did not differ between the groups. Children who received dimenhydrinate had significantly less POV both inhospital (10%) and overall (30%) than those who received placebo (in-hospital 38%, P < 0.008; overall 65%, P < 0.003). The times to arousal and discharge from the hospital did not differ between the two groups. Dimenhydrinate (0.5 mg/kg) is an effective, safe, and inexpensive antiemetic in children undergoing strabismus surgery. It significantly reduces the incidence of vomiting for 24 h postoperatively and is not associated with prolonged sedation or other adverse effects.

[Peroperative risks in cerebral aneurysm surgery]. / Risques peropératoires lors de chirurgie cérébrale anévrismale.

The perioperative complications associated with cerebral aneurysm surgery require a specific anaesthetic management. Four major perioperative accidents are discussed in this review. The anaesthetic and surgical management in case of rebleeding subsequent to the re-rupture of the aneurysm is mainly prophylactic. It includes haemodynamic stability assurance, maintenance of mean arterial pressure (MAP) between 80-90 mmHg during stimulation of the patient such as endotracheal intubation, application of the skull-pin head-holder, incision, and craniotomy. The aneurysmal transmural pressure should be adequately maintained by avoiding an aggressive decrease of intracranial pressure. Once the skull is open, the brain must be kept slack in order to decrease pressure under the retractors and avoid the risks of stretching and tearing of the adjacent vessels. If, despite these precautions, the aneurysm ruptures again. MAP should be decreased to 60 mmHg and the brain rendered more slack, in order to allow direct clipping of the aneurysm, or temporary clipping of the adjacent vessels. The optimal agents in this situation are isoflurane (which decreases CMRO2), intravenous anaesthetic agents (inspite their negative inotropic effect, they may potentially protect the brain) and sodium nitroprusside. Vasospasm occurs usually between the 3rd and the 7th day after subarachnoid haemorrhage. It may be seen peroperatively. The optimal treatment, as well as prophylaxis, is moderate controlled hypertension (MAP > 100 mmHg), associated with hypervolaemia and haemodilution, the so-called triple H therapy, with strict control of the filling pressures. Other beneficial therapies are calcium antagonists (nimodipine and nicardipine), the removal of the blood accumulated around the brain and in the cisternae, and possibly local administration of papaverine. Abrupt MAP increases are controlled in order to maintain adequate aneurysmal transmural pressure. Beta-blockers, local anaesthetics administered locally or intravenously, a carefully titrated level of anaesthesia, a maintained volaemia play a protective role. Cerebral oedema is sometimes already present at the opening of the skull or may arise later, due to a high pressure under the retractors, to the surgical manipulations of the brain or to brain ischaemia subsequent to temporary clipping. Its treatment is aggressive, with intravenous agents, mannitol, deep hypocapnia and/or lumbar drainage. Prophylaxis, according to the "brain homeostasis concept", is the preferred method to avoid these four peroperative accidents. It includes normal blood volume, normoglycaemia, moderate hypocapnia, normotension, soft manipulation of the brain and optimal brain relaxation.