Microsurgical treatment for unruptured intracranial aneurysms: a modern single surgeon series.

With the rise of endovascular treatments for the management of unruptured intracranial aneurysms (UIAs), advances in microsurgical techniques are underrepresented in modern surgical series, which largely consist of patients with aneurysms unfit for coiling. We report a modern series of microsurgical treatment for UIAs performed by a single surgeon as the preferred treatment modality. We retrospectively reviewed the charts of all patients with UIAs treated by the senior author with microsurgical clipping over an 11-year period. Procedure-related mortality, major neurologic morbidity (modified Rankin Score 3-5), complications, and persistent neurologic deficits were recorded. Risk factors for persistent neurologic deficits and major morbidity or mortality were analyzed using multivariate logistic regression analysis. We identified 329 patients with 400 UIAs treated in 353 surgeries. The average age was 52 years, 80% of patients were women, and 13% had a previous subarachnoid hemorrhage. The average aneurysm size was 7 mm and 92% were in the anterior circulation. The mean follow-up was 15 months (range 0.5-125). There was one procedure-related death (0.3%), and two patients suffered major morbidity (0.6%). Twenty procedures (5.6%) resulted in a persistent neurologic deficit. Risk factors for death and major morbidity were increasing age and posterior circulation, while risk factors for persistent neurologic deficits were increasing aneurysm size and posterior circulation. We conclude that microsurgical clipping is safe, effective, and should be given strong consideration as the primary treatment modality for younger patients with small to medium sized UIAs in the anterior circulation.

Perioperative anaesthetic management of high-order repeat caesarean section: audit of practice in a university-affiliated medical centre.

BACKGROUND: High-order (five or more) repeat caesarean sections (HORCS) are associated with increased rates of placenta praevia, placenta accreta and peripartum hysterectomy and prolonged surgical time secondary to intra-abdominal adhesions. This study summarizes our experience in the anaesthetic management of HORCS. METHODS: The files of all parturients undergoing HORCS between January 1995 and August 2007 were reviewed to determine surgical times, rates and causes of conversion from neuraxial to general anaesthesia and the need to supplement neuraxial anaesthesia with intravenous sedation. RESULTS: Parturients (n=108) were 35+/-4.5 years old with a gestational age of 37.5+/-1.5 weeks, weighed 88+/-20 kg and had undergone 6+/-1 caesarean sections. Eighty-six (80%) were elective. Initial anaesthetic techniques included spinal (n=80, 74%), epidural (n=9, 8%), combined spinal-epidural (n=6, 6%) and general anaesthesia (n=13, 12%). Surgery lasted 38+/-19 min (median 34, range 9-120). Fourteen parturients (13%) underwent intraoperative manipulations other than caesarean section, including three hysterectomies for haemorrhage (two placenta accreta, one praevia). There were no ruptures or dehiscences of the uterine scar, intraoperative bladder/ bowel injuries or re-explorations. Apgar scores <9 at 1 (n=9, 13%) and 5 (n=6, 5%) min were related to non-anaesthetic causes. Anaesthesia was converted from neuraxial to general in five cases (5/95, 5%) but only two were due to haemorrhage. No epidural top-up doses or intravenous sedatives/analgesics were required for spinal anaesthesia. CONCLUSION: HORCS is not necessarily an indication for general anaesthesia provided uterine and placental abnormalities are sought preoperatively. In our practice single-shot spinal anaesthesia sufficed for uncomplicated HORCS.

Isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase/Akt signalling.

BACKGROUND: Isoflurane and other volatile anaesthetics have a cardioprotective effect and limit myocardial infarct size to the same extent as ischaemic preconditioning. Phosphatidylinositol-3-kinase (PI3K) was found to play a key role in myocardial protection by ischaemic preconditioning. The aim of the present investigation was to evaluate whether isoflurane-induced myocardial preconditioning is dependent on PI3K signalling. METHODS: Using a model of regional myocardial ischaemia and reperfusion, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia followed by 120 min of reperfusion. The rabbits were randomly assigned to one of the following six experimental groups: sham-operated controls (n=5); ischaemia and reperfusion controls (n=8); isoflurane preconditioning (n=8); a PI3K inhibitor, wortmannin (0.6 mg kg(-1) i.v.) + isoflurane (n=8); and wortmannin+ischaemia and reperfusion (n=8). An additional control group of sham operation+ wortmannin (n=5) was also included. Myocardial injury was assessed by measuring the serum concentration of the MB fraction of creatine kinase (CK-MB) and infarct size was assessed by 2,3,5-triphenyl tetrazolium chloride staining. Phosphorylation of Akt, a downstream target of PI3K, was assessed by western blotting. RESULTS: Isoflurane preconditioning was seen as reduced infarct size compared with control animals: 24 (4) and 41 (5)% respectively (P<0.05). Wortmannin inhibited this cardioprotective effect with myocardial infarct size at 44 (3)% (not significant). Akt phosphorylation was increased after isoflurane preconditioning, but administration of wortmannin blocked this effect. CONCLUSIONS: Our data demonstrate that isoflurane protects the heart against ischaemia and decreases myocardial infarction by activation of PI3K.

Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit.

BACKGROUND: Reactive oxygen species are an important mediator in isoflurane-induced myocardial preconditioning. However, hydroxyl radicals are also released during reperfusion after regional ischaemia. The purpose of the present study was to test whether ischaemic preconditioning and isoflurane would influence the production of hydroxyl radicals during reperfusion. METHODS: After i.v. administration of salicylate 100 mg kg(-1) and a 30 min stabilization period, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia and 2 h of reperfusion. Ischaemic preconditioning was elicited by 5 min ischaemia followed by 10 min reperfusion (before the 40 min ischaemia). In another group, isoflurane (2.1%) was administered for 30 min, followed by 15 min washout, before the long ischaemia. Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. We quantified the level of OH-mediated conversion of salicylate to its dihydrobenzoate derivatives (2,3- and 2,5-DHBAs). Normalized values of the DHBAs (ng DHBA per mg salicylate) were calculated. RESULTS: Mean (se) infarct size was 57 (6)% of the risk area in the untreated controls. This was significantly smaller in the ischaemic preconditioning and isoflurane groups: 22 (5) and 23 (6)% respectively. At 10 min of reperfusion, ischaemic preconditioning limited the mean increase in 2,3-DHBA to 24% from baseline, compared with 81% in control and 74% in the isoflurane group. Normalized 2,5-DHBA was maximally increased by 75% in the untreated group, 4 min after reperfusion. Ischaemic preconditioning significantly inhibited this increase (24% increase from baseline, P<0.01). However, the increase observed in the isoflurane group was not different from control (71%). CONCLUSIONS: As already known, ischaemic preconditioning and isoflurane markedly reduced infarct size. However, only ischaemic preconditioning decreased postischaemic production of hydroxyl radicals. These different effects suggest different protective mechanisms at the cellular level.

Ischaemic preconditioning but not isoflurane prevents post-ischaemic production of hydroxyl radicals in a canine model of ischaemia-reperfusion.

BACKGROUND AND OBJECTIVE: Isoflurane has been shown to mimic ischaemic preconditioning (IPC). The protective effect of IPC, or applying isoflurane or perfusion with the 'push-pull' complex zinc-desferrioxamine (Zn-DFO) in the canine heart, was investigated. METHODS: Thirty minutes after salicylate administration (100 mg kg(-1)) the heart was exposed. All dogs were subjected to a 10 min left anterior descending artery occlusion followed by 2 h of reperfusion. In Group I (n = 9) isoflurane (2.5%) was administered 10 min prior to and during ischaemia. In Group II (n = 8), IPC was elicited by 5 min coronary artery occlusion, followed by 5 min of reperfusion, prior to the 10 min ischaemia. In Group III (n = 9) Zn-DFO (2.5 mg kg(-1)) was given 10 min prior to ischaemia. The effects of these interventions were compared to control (n = 10). Coronary sinus blood concentrations of salicylate, 2,3-dihydroxybenzoic acid (DHBA), lactate, pH and oxygen content were monitored. RESULTS: In the control group, 2,3-DHBA increased by 32% above the pre-ischaemic value (P < 0.05). In contrast, in the IPC hearts, a significant decrease in the production of 2,3-DHBA was observed (40% lower than baseline, P < 0.01). In the isoflurane group only a 13% (and non-significant) decrease was noticed. In the Zn-DFO group a 33% decrease was found (P < 0.01). The increase in lactate concentrations in the IPC and Zn-DFO groups was significantly smaller than that of control and isoflurane groups. CONCLUSIONS: IPC protected the heart against the deleterious effects of reperfusion, possibly by amelioration of the level of oxygen-derived reactive species, and the complete inhibition of reactive hydroxyl radical production. Isoflurane did not prove to be as effective in reducing the free radical damage.

Complicated endoscopic pediatric procedures using deep sedation and general anesthesia are safe in the endoscopy suite.

BACKGROUND: Complicated upper and lower endoscopic procedures of the gastrointestinal tract are performed in children for a variety of diagnostic and therapeutic reasons. Unlike adult patients, who receive conscious sedation, children usually require deep sedation (DS) or general anesthesia (GA). The aim of this study is to assess the safety parameters of complicated endoscopic procedures under DS or GA performed in children in the endoscopy suite rather than in the operating theatre. METHODS: Between May 1997 and December 2002, 296 patients (mean age 4.5 years, range 3 weeks to 16 years), defined as ASA I-III, underwent either DS or GA for endoscopic foreign body extraction, endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous endoscopic gastrostomy (PEG) insertion. ASA physical status I was found in 15%, II in 57% and III in 28%. The pathologies included neuromuscular diseases, genetic syndromes, nesidioblastosis, biliary atresia, hematologic, respiratory (cystic fibrosis) and cardiac disorders. Propofol was the drug of choice (63%) followed by a combination of propofol and midazolam (16%). RESULTS: Transient desaturation (O2 saturation <90%) was the only complication recorded in 21/296 (7.09%) patients. Only two patients with severe respiratory underlying disease were hospitalized for follow-up for a 24-h period. CONCLUSIONS: The use of DS and GA for complicated endoscopies in a moderately high-risk pediatric population was found to be safe. The very low complication rate found in this study suggests that complicated pediatric patients can be managed successfully outside the operating theatre, provided that all the safety criteria for ambulatory DS or anesthesia are present.

[The use of conscious sedation versus general anesthesia in modern dentistry: rising ethical dilemmas].

Conscious sedation and general anesthesia have been in the use of the dental profession since the first half of the 19th century. Although seemingly appealing to use due to alleviation of pain and anxiety induced by the dental treatment, the alteration of consciousness level of dental patients is not without risk. Morbidity and mortality due to dental treatment performed under general anesthesia were investigated at the last decades of the 20th century. The mortality rates found in these investigations were surprisingly high comparing to researches of morbidity and mortality due to other medical procedures, performed under general anesthesia. Therefore, although general anesthesia is sometimes the only way to treat certain patients, maintaining strict indications for dental treatment under general anesthesia is necessary. Conscious sedation was found as a safer alternative for achieving a level of consciousness enabling dental treatment in those patients who are unable to receive treatment in normal dental clinic settings. We therefore believe that conscious sedation should be the golden standard for the treatment of those patients. The practicing of dentistry in patients who have need of dental treatment under special settings such as general anesthesia and sedation raises ethical dilemmas to the caregiver. The following review will summarize the available data on morbidity and mortality due to dental treatment given under general anesthesia and conscious sedation. The ethical questions arising from their practicing will be discussed and some answers shall be proposed.

Manipulations in glycogen metabolism and the failure to influence infarct size in the ischaemic rabbit heart.

BACKGROUND AND OBJECTIVE: Myocardial ischaemic preconditioning is characterized by a reduction in the rate of glycolysis. Brief myocardial ischaemia also reduces the glycogen content of the heart. The first objective was to determine whether augmenting glucose oxidation by activation of the pyruvate dehydrogenase complex would prevent the infarct limitation of ischaemic preconditioning. The second part of the study evaluates whether glycogen depletion before ischaemia mimics the infarct-limiting effect of ischaemic preconditioning. METHODS: Dichloroacetate (300 + 150 mg kg(-1)), an activator of the pyruvate dehydrogenase complex, was administered intravenously in the anaesthetized open-chest rabbit. All animals underwent 45 min of regional ischaemia and 3 h of reperfusion. Ischaemic preconditiong was elicited by 5 min of coronary occlusion. Control rabbits, those with ischaemic preconditioning with no dichloroacetate, received a saline vehicle. An isolated perfused rabbit heart model was employed to test the second hypothesis. Hearts were depleted of glycogen by perfusing them with a substrate-free buffer. Infarction was assessed by triphenyl tetrazolium chloride and area at risk determined with fluorescent particles. RESULTS: (a) Pyruvate dehydrogenase complex activation experiments. Treatment with dichloroacetate alone did not alter infarct size (58 +/- 7% control vs. 60 +/- 5% dichloroacetate). Addition of dichloroacetate did not attenuate the infarct-limiting effect of ischaemic preconditioning as evidenced by a similar reduction in infarct size in the ischaemic preconditioning group (22 +/- 5%) and in the ischaemic preconditioning + dichloroacetate group (27 +/- 7%). (b) Glycogen depletion experiments. Compared with control hearts with a normal glycogen content (4.84 +/- 0.15 mg g(-1) wet weight), glycogen depleted and ischaemic preconditioning hearts had reduced glycogen content before ischaemia (2.15 +/- 0.26, 1.62 +/- 0.17 mg g(-1) wet weight, respectively; P < 0.01). Glycogen depletion did not reduce infarct size: 25.0 +/- 4.5% cf. 27.9 +/- 3.4% in the control group. However, ischaemic preconditioning resulted in a significant reduction of infarct size (11.5 +/- 2.3% vs. 27.9 +/- 3.4% control; P < 0.01). CONCLUSIONS: Augmentation of oxidative glycolysis by dichloroacetate in in situ rabbit hearts does not alter the effect of ischaemic preconditioning, and glycogen depletion in the isolated rabbit heart does not influence infarct size after subsequent coronary occlusion.

Propofol does not modify the hemodynamic status of children with intracardiac shunts undergoing cardiac catheterization.

Immobility and cardiovascular stability are required for cardiac catheterization. Pediatric patients need a type of sedation that also allows spontaneous ventilation without supplemental oxygen. Propofol has been adequate in hemodynamically stable patients with congenital heart disease undergoing cardiac catheterization. However, mild systemic hypotension caused by propofol may increase a preexisting right-to-left shunt. The aim of this study is to evaluate, in pediatric patients scheduled for cardiac catheterization, the effects of propofol on systemic and pulmonic circulations. Fifteen patients aged 18 months to 9 years were studied. After a fast of 4-6 hours for solid food, the patient arrived at the cardiac catheterization suite, where an IV catheter was placed. Usual monitoring was used. For sedation, without supplemental oxygen, patients received 1 mg/kg of fentanyl followed by propofol (1-2 mg/kg) titrated to immobility during preparation of the groin. A continuous infusion of propofol (100 mg/kg/min) was also started to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations, and pressures, were recorded; Qp and Qs were calculated. The same set of data was re-corded 4 minutes after discontinuation of propofol and when the patient was responding to tactile stimuli. Despite lower pressures during propofol infusion, as compared with those pressures measured after discontinuation of propofol, the extent of the intracardiac shunt remained unchanged. Propofol seems to be an adequate sedative agent for pediatric patients undergoing cardiac catheterization, including those with intracardiac shunts.

Perioperative myocardial ischemia in cataract surgery patients: general versus local anesthesia.

Patients having cataract surgery are usually elderly and have risk factors for ischemic heart disease. We sought to determine the incidence of perioperative myocardial ischemia in patients having cataract surgery and compare the influence of local anesthesia (LA) and general anesthesia (GA). Eighty-one patients undergoing cataract surgery with at least two risk factors for ischemic heart disease were monitored continuously for 24 h by using electrocardiogram leads II and V5 and a Holter recorder (Medilog 4500, Oxford Ltd, UK). Patients were randomly allocated to two groups, either LA (n = 39) or GA (n = 42). In the LA group, a peribulbar block was performed, whereas a similar block was performed in the GA group after tracheal intubation. The study demonstrated that cataract patients suffered from a frequent incidence of perioperative myocardial ischemia (31%). There was no difference in the incidence rate between the groups: 12 of 39 in the LA group and 13 of 42 in the GA group (P: = NS). However, the number of ischemic episodes was significantly increased in the GA group (18 vs. 13 in the LA group) (P<0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P<0.01). All intraoperative ischemic events were associated with tachycardia (> or =20% of baseline), whereas postoperative ischemic changes were mostly independent of heart rate. Only one of the ischemic patients (in the GA group) was admitted as a result of intractable chest pain. There were significantly less intraoperative episodes in the LA group, suggesting that LA may be safer than GA in patients during this type of surgery.

The effect of clonidine premedication on hemodynamic responses to microlaryngoscopy and rigid bronchoscopy.

The usual hemodynamic response to laryngoscopy and bronchoscopy is an increase in heart rate and arterial blood pressure. Previous work has reported that 10%-18% of the patients develop ischemic ST segment changes during the procedure. Therefore, we performed a prospective, randomized, double-blinded study in 36 patients scheduled for elective microlaryngeal and bronchoscopic surgical procedures to evaluate the effects of 300-microg oral clonidine premedication (n = 18) or placebo (n = 18) on the hemodynamic alterations and the incidence of perioperative myocardial ischemic episodes. Myocardial ischemia was assessed by using continuous electrocardiographic monitoring, beginning 30 min before, and lasting until 24 h after the operation. During the procedure, patients receiving placebo exhibited a significant increase (mean +/- SD) in arterial blood pressure (the systolic increasing from 137+/-11 to 166+/-17 mm Hg, the diastolic increasing from 80+/-11 to 97+/-14 mm Hg) and heart rate (increasing from 79+/-15 to 97+/-12 bpm) compared with the baseline and with the clonidine group. A dose of 300-microg clonidine blunted the hemodynamic response to endoscopy. Ventricular arrhythmias were more frequent in patients who were not premedicated with clonidine. Two patients in the control group, but none in the clonidine group, had evidence of myocardial ischemia. These data should encourage routine premedication with clonidine in patients undergoing microlaryngoscopic and bronchoscopic procedures.

Hypoxia induces activation of a N-methyl-D-aspartate glutamate receptor-protein kinase C pathway in the dorsocaudal brainstem of the conscious rat.

To study in vivo phosphorylation of N-methyl-D-aspartate (NMDA) glutamate receptors and the recruitment of protein kinase C isoforms during acute hypoxia, dorsocaudal brainstem lysates were harvested from conscious rats exposed to either room air or hypoxia (10% O2 for 5 and 15 min). Increased phosphorylation of the NR-1 subunit at serine residue 896 occurred during hypoxia and was blocked by pre-treatment with MK-801. Immunoblots of soluble and particulate fractions revealed subcellular translocation for PKC-beta, -gamma, -delta, -epsilon, and -iota during hypoxia with no changes in PKC-alpha, -mu, and -zeta. Translocation of PKC-beta, -delta and -epsilon was selectively attenuated following MK-801. We demonstrate that hypoxia leads to PKC-mediated activation of NMDA receptors in the brainstem, and that PKC-beta, -delta and -epsilon are the most likely candidates for NR-1 phosphorylation.

Anaesthetic management of a patient undergoing reoperation for pathway obstruction after fontan operation.

Since 1968, the Fontan operation, or its various modifications, have provided a functional correction in an increasingly complex spectrum of congenital heart malformations.1.2 These procedures have gained wide acceptance because of very good intermediate and longterm results2. However, as survival increases, follow up of these patients has shown more prevalent reoperations for obstruction of the surgically created corrective pathway.3 perioperative management of these patients requires an understanding of the unique anatomic and physiologic changes occurring in this condition. In this report, we review our anaesthetic management of a patient who underwent reoperation for thrombotic occlusion of the conduit from a previous Fontan procedure.

Coronary Artery Bypass Grafting without Cardiopulmonary Bypass: Improvement in Cardiac Function Following Enflurane Anaesthesia during Coronary Occlusion.

Severe adverse effects, especially neurologic complications after cardiopulmonary bypass have lead to the development of techniques for performing coronary artery bypass graft surgery without cardiopulmonary bypass. Laboratory and clinical studies confirmed the positive role of enflurane anaesthesia in preventing myocardial dysfunction following an ischaemic interval. The aim of this study was to evaluate the haemodynamic response to enflurane anaesthesia during single graft coronary bypass surgery without cardiopulmonary bypass. Twenty one patients were divided randomly into two groups: control and enflurane groups. Haemodynamic parameters and those derived from a pulmonary artery catheter were recorded and analysed. In the enflurane group, the amount of fentanyl administered was considerably less than in the control group: 25.7 +/- 3.8 microg/kg vs 36.8 +/- 1.6; p=0.03. The mean arterial pressure during enflurane administration was lower than in control group, but the difference was not significant. Despite a dearease in left ventricular function during the performance of the anastomosis in the enflurane group, a significant recovery was noted after 20 minutes of reperfusion: cardiac index increased from 1.4 +/- 0.1 to 1.85 +/- 0.1 L/min/m2 and left ventricular stroke work index from 15.8 +/- 1.1 to 27.7 +/- 6.7 g.m.m2 . In the control group, the deterioration in cardiac function observed during the graft anastomosis did not recover till the end of the surgical procedure. We conclude that enflurane anaesthesia may be a positive addition to fentanyl-based anaesthesia by improving myocardial function following CABG without bypass surgery.

Halothane modifies oxygen free radical activity on the voltage-sensitive calcium channels in canine myocardial membranes.

BACKGROUND: The functional derangements in the myocyte cell membrane, the sarcolemma, during short myocardial ischaemia and reperfusion are attributed to excessive influx of Ca2+ ions via the voltage-sensitive calcium channels (VSCC) and to the free radical-related injury. However, it is unclear whether the primary changes in the VSCC should be attributed to the ischaemic effect or to free radical action on channel constituents. Under these circumstances of ischaemia and reperfusion, volatile anaesthetics have exhibited protective properties on the myocardium. The present study is aimed at characterizing the effect of artificially-generated oxygen free radicals on the VSCC in canine sarcolemma, independently of the effect of ischaemia, and the effect of halothane on the membranes during the surge of the free radicals. METHODS: Selective production of free radicals (O2-, CO2-) was made by gamma irradiation of isolated sarcolemma membranes with 137 Cesium (Cs), in the presence of 20 mM sodium formate. Control studies were performed without formate in the aqueous solution. In an additional group, liquid halothane (3 microl. 1.9 vol%) was added to the sarcolemma / formate preparation immediately prior to irradiation. The effects of free radicals on the VSCC was evaluated by redioligand binding studies of the calcium channel blocker [3H] isradipine to the sarcolemma. RESULTS: In six control studies, the rediolytic aqueous species produced by 137 Cs irradiation resulted in unchanged [3 H] isradipine binding. In the presence of formate [n=9], the free radicals have caused a 23% to 25% decrease, both, in density and dissociation constant (P=0.05) of [3 H]isradipine to the VSCC binding sites. When superoxide radicals were generated in the presence of 1.9% halothane and formate (n=6), a significant increase in maximal binding capacity (by 55% +/- 2; P<0.01) and in the dissociation constant (by 209% +/- 35, P<0.01) occurred. CONCLUSION: Oxidative free radicals which are generated by gamma irradiation exerted minimal changes on the normal function of the VSCC as reflected by the non-significant changes in [3 H] isradipine specific binding. Introduction of halothane into free radical generating system causes acute perturbations to the VSCC kinetics, and does not provide protection to the cardiac membranes.