Prediction of Poor Response to Modified Neuroleptanalgesia with Midazolam for Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Modified neuroleptanalgesia (m-NLA) with midazolam is often used for sedation and analgesia during endoscopic submucosal dissection (ESD) for gastrointestinal neoplasia. However, interruption due to poor response to midazolam is often experienced during ESD for esophageal squamous cell carcinoma (ESCC) because most patients with ESCC have a history of heavy alcohol intake. We examined the incidence and risk factors for poor response to m-NLA with midazolam and pethidine hydrochloride. METHODS: This retrospective cross-sectional study was conducted at a single institution. Between April 2007 and July 2013, 151 patients with superficial ESCC who underwent ESD under sedation using m-NLA with midazolam and pethidine hydrochloride were enrolled. Poor response to sedation was defined as the use of a second drug when Ramsay Sedation Score 1-2. RESULTS: Poor response to sedation occurred in 66.2% patients. Most cases of poor response were controlled by using additional flunitrazepam. Multivariate logistic regression analysis showed that cumulative alcohol intake and major specimen size were independent risk factors for poor response to sedation (OR 3.63, 95% CI 1.20-10.99, and OR 3.23, 95% CI 1.26-8.25). CONCLUSION: Our study indicated that cumulative alcohol intake and major specimen size were associated with poor response to m-NLA with midazolam and pethidine hydrochloride.

[Clinical application of brain hypothermia therapy for acute brain insults].

Brain hypothermia therapy has been expected to lead to good neurological outcome in acute brain insults. There are a few positive results which have been proven by multicenter randomized clinical trials (RCT) in the cardiopulmonary arrest (CPA) in patients with ventricular fibrillation. Among these clinical trials, early application of hypothermia, maintenance of cerebral blood flow during hypothermia therapy and prevention of quick rewarming are pointed out to result in good outcome from clinical experiences. For brain hypothermia therapy to become an effective method for acute brain insults, indications, brain oriented intensive cares and biomarkers for the therapy must be established. RCT in acute brain insults beside CPA victims are needed in the near future.

Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus.

BACKGROUND: Postoperative cognitive dysfunction is being increasingly reported as a complication. The authors investigated the role of cytokine-mediated inflammation within the central nervous system in the development of cognitive dysfunction in a rat model. METHODS: Adult rats were subjected to neuroleptic anesthesia (20 microg/kg fentanyl plus 500 microg/kg droperidol, intraperitoneal) for splenectomy or no surgery. On postanesthetic days 1, 3, and 7, cognitive function was assessed in a Y maze. To evaluate the immune response in the hippocampus, the authors measured glial activation, as well as transcription and expression of key proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. To determine propensity for apoptosis, they measured expression of Bax and Bcl-2. RESULTS: Cognitive function in splenectomized animals was impaired at days 1 and 3 after surgery compared with cognitive function in nonanesthetized rats. At all times, anesthetized rats that were not subjected to surgery were no different from control rats. Glial activation was observed in the hippocampus only in splenectomized rats at postsurgery days 1 and 3. Interleukin-1beta messenger RNA (mRNA) was significantly increased at postsurgery days 1 and 3, with an increase in protein expression detected on day 1. There was a significant increase in tumor necrosis factor-alpha mRNA on day 1 after surgery, although this was not associated with an increase in protein expression. The ratio of Bcl-2:Bax was significantly decreased in the splenectomized animals. CONCLUSION: These results suggest that splenectomy performed during neuroleptic anesthesia triggers a cognitive decline that is associated with a hippocampal inflammatory response that seems to be due to proinflammatory cytokine-dependent activation of glial cells.

[Comparative analysis of antiarrhythmic and proarrhythmogenic effects of drugs for neuroleptanalgesia, ataralgesia, and antidepranalgesia in experimental acute myocardial infarction].

Proarrhythmogenic and antiarrhythmic effects of drugs for neuroleptanalgesia (NLA), ataralgesic (ATA) and antidepranalgesia (ADA) in chronic experiments on sleepless rabbits with acute myocardial infarction, with and without tachyarrhythmias, were studied using ECG, intraventricular electromanometry and tetropolar rheography. NLA (phentanylum, 1 microg/kg + droperidol, 5 microg/kg), ADA (pyrazidole, 1 mg/kg + tramal, 1 mg/kg) and ATA (diazepam, 1 mg/kg + promedol 0.5 mg/kg) produce antiarrhythmic effect with maximum manifestation of NLA on the 3rd day, and of ATA and ADA on 3-5th day. This medication increased blood supply and contractility of ischemic myocardium. Proarrhythmogenic effects of this medication were not observed.

[Droperidol causes multifocal ventricular dysrhythmias].

We report a case of ventricular chaotic arrhythmia after droperidol administration. A 49-year-old woman with chronic renal failure receiving hemodialysis, was scheduled for total hysterectomy under general anesthesia. General anesthesia was induced with thiopental 200 mg, fentanyl 0.1 mg and vecuronium 5 mg for endotracheal intubation. Anesthesia was maintained with 1% isoflurane and 60% nitrous oxide in oxygen. Droperidol 10 mg was injected for neuroleptanalgesia. After two minutes, ventricular chaotic arrhythmia occurred. Lidocaine 80 mg was injected. General anesthesia was stopped. After two minutes, arrhythmia disappeared. Several reports suggest that patients with preexisting conduction defects or prolonged QTc interval may be at risk to develop ventricular arrhythmias after droperidol administration. Administration of droperidol may have exaggerated prolongation of QTc interval.

[Qualitative comparison of modified neurolept-, balanced and intravenous anesthesia. 2. Results of a clinical study, 1992]. / Qualitätsvergleich von modifizierter Neurolept-, balancierter und intravenöser Anästhesie. Teil 2. Ergebnisse der Krefelder Studie 1992.

The safety and tolerance of neuroleptanaesthesia (NLA), balanced anaesthesia (BAL), and intravenous anaesthesia with propofol (IVA) were analysed for the first time in a prospective, randomised clinical trial. METHODS. In all, 1318 surgical patients received either NLA, BAL, or IVA. Patients who had regional anaesthesia, were aged under 18 years, or were non-cooperative or vitally threatened (ASA class i.v. to V) did not participate in the study. Premedication and anaesthetic course were set up at a standard of 30% oxygen and 70% nitrous oxide. Incidents, events, and complications due to anaesthesia were obtained (IEC key of the German Society of Anaesthesia and Critical Care Medicine, DGAI). Furthermore, postanaesthetic alertness based on specific recovery tests and the quality of anaesthesia from the patient's viewpoint, rated by patient questionnaires from the DGAI were evaluated. All parameters were calculated and checked for statistical significance using the chi-square test. RESULTS AND DISCUSSION. The groups were broadly comparable with respect to age (P = 0.91), ASA class (P = 0.42), preoperative blood pressure (P = 0.36), and length of anaesthesia (P = 0.82). The anaesthesia, which averaged 103 min, comprised the following regimens: (1) NLA: 7.1 mg droperidol and 0.008 mg/kg body weight fentanyl, (2) IVA: 493.4 mg propofol and 0.004 mg/kg body weight fentanyl, and (3) BAL: 2.6 mg droperidol and 0.004 mg/kg body weight fentanyl with 0.4 vol.% isoflurane. With respect to anaesthetic risk, the following reactions were observed: the use of NLA led to a high incidence of tachycardia (P = 0.001), arrhythmias (P = 0.05), and hypertensive reactions (P = 0.001), whereas in the IVA group only hypotension (P = 0.0001) occurred. However, after the use of BAL none of the aforementioned complications were detectable to any considerable degree. Similarly, patients who had cardiac disease showed greater IEC changes after the use of NLA than after BAL or IVA (P = 0.02) (Tables 1 and 2). The heart rates and blood pressures during BAL and IVA were extremely stable, and therefore, vasoactive therapy was required considerably less in comparison to NLA (P = 0.001) (Table 4). Recovery after the use of IVA was strikingly rapid: the patient's responsiveness, orientation, and ability to concentrate was significantly better than after the other anaesthetic regimen (P = 0.01) (Table 5). With regard to the typical discomforts after anaesthesia, IVA was highly superior to BAL and NLA: nausea (P = 0.0003) and retching (P = 0.03) hardly ever occurred (Table 6). Due to the tolerable manner of waking up and rapid return of orientation and the ability to concentrate, IVA was highly favoured by the patients (P = < 0.01) (Table 7). CONCLUSION. The present results show clear clinical advantages of BAL and IVA in contrast to neuroleptanaesthesia. Due to the very low incidence of side effects such as nausea and vomiting IVA was highly recommended by the patients, at least in part because of the rapid recovery time.

[Laparoscopic cholecystectomy: evaluation of intraoperative complications with respect to 2 different kinds of anesthesia]. / Colecistectomia laparoscopica: stima di alcune complicanze perioperatorie in rapporto a due differenti metodiche di anestesia.

Two anaesthetic managements for elective laparoscopic cholecystectomy were compared in 64 patients in order to investigate some perioperative complications: 1) bowel distension during surgery. 2) recovery from anaesthesia. 3) post-surgery incidence of emesis and pain. In addition, the quality of postoperative peristalsis as well as the time of dimissal were recorded. Group I (n = 30) was treated with NLA in N2O-O2 and Group II (n = 34) received propofol plus fentanyl in air-O2. Bowel distension, evaluated by surgeon at 15 min intervals throughout the operation was similar in both the groups as well as postoperative peristalsis recuperation. During the first 12 hours after laparoscopy no differences were found at any times of observation in the incidence or severity of emesis and pain between the two different anaesthesia patients. In subjects which were given propofol the psychomotor recovery was more rapid than after NLA, particularly during the first 6 hours after surgery. The patients were discharged between 36-48 hours following the operation independently from anaesthetic management. It is concluded that both the anaesthetic techniques provide similar intra/postoperative conditions, except the early recovery that is more rapid for the propofol patients. The overall frequency of emesis and pain was rather high in both the groups, suggesting a routine medication with analgesics and antiemetics.

[Quality comparison of modified neurolept-, balanced and intravenous anesthesia. 1. Study design and patient analysis of the Krefelder study 1992]. / Qualitätsvergleich von modifizierter Neurolept-, balancierter und intravenöser Anästhesie. Teil 1. Studiendesign und Patientenanalyse der Krefelder Studie 1992.

The choice of appropriate anaesthesia in a more or less seriously ill patient requires detailed information on the risk and tolerance of each specific anaesthetic regimen. The objective of this prospective, randomised clinical trial was to test the hypothesis that three regimens of general anaesthesia--neurolept-(NLA), balanced (BAL), and intravenous propofol anaesthesia (IVA)--differ with regard to safety and comfort. The criteria for the intraoperative safety and postoperative comfort of the patients were the incidents, events and complications (IEC) that required medical treatment as well as the evaluation of postoperative complaints by the patients according to the IEC list and patient questionnaires of the German Society of Anaesthesia and Critical Care Medicine (DGAI). METHODS. The study duration was about 4 months, from January to April 1992. During this period the patients of all nine operative departments of the hospital received strictly randomised NLA, BAL, or IVA. Patients who had regional anaesthesia or were not capable of understanding the German language, were nonco-operative, or were seriously ill (ASA class IV to V) as well as children under 18 years of age did not participate in the study. All eligible patients provided their informed consent. ANAESTHESIA. For premedication 10 mg chlorazepate was administered the night before and on the day of surgery. Anaesthesia was conducted under normoventilation using a mixture of 70% nitrous oxide and 30% oxygen. NLA patients were induced intravenously with 0.2 mg/kg body weight etomidate and received 0.005 mg/kg fentanyl and 0.07 mg/kg droperidol before the start of surgery. The repetition dose was 0.2 mg fentanyl and 2.5 mg droperidol. In the BAL patients the dose of fentanyl and droperidol was reduced to 50% due to the addition of isoflurane up to 1 vol. %. IVA patients received 2 mg/kg propofol over 3 min followed by an infusion of 3-5 mg/kg per hour together with 0.2 mg fentanyl/h. Neuromuscular blockade was accomplished with vecuronium 0.1 mg/kg. If the blood pressure and heart rate increased by more than 20% of preoperative values, analgesia was reinforced by an additional fentanyl dose. Anaesthesia was subsequently enhanced by increasing the neurolept/propofol/isoflurane dose by up to 50%. DATA COLLECTION. The following parameters were registered: patients' personal data and physical condition according to ASA classification; the grade of risk according to the Munich risk checklist; the frequency of IEC during surgery; the patients' permanent medications; postanaesthetic vigilance and recovery; the acceptance of the assigned anaesthetic by the physician; the cost of the anaesthetic used; and pre- and post-operative complaints as well as the assessment of anaesthesia by the patient. The statistical evaluation was performed using the chi-square test. RESULTS. A total of 1,346 patients were enrolled in the study; 28 (2%) were excluded because the treatment protocol was changed by the anaesthesiologist. Seventy per cent were recruited from general, gynaecologic, or otorhinolaryngologic surgery. The three anaesthetic regimens (NLA, BAL, and IVA) were used in other departments with the same frequency with the exception of ophthalmology and urology (P > 0.1) (Fig. 1). Of the 1,318 eligible patients, 443 received NLA, 443 BAL, and 432 IVA (P = 0.8). The distribution of the various parameters was surprisingly similar among the three groups: the average age was 50 years (P = 0.91), body weight 71 kg (P = 0.33), reference or initial blood pressure 130/80 mm Hg (P = 0.36), average time of anaesthesia 103 min (P = 0.82), and all had the same risk score (P = 0.42). Sixty per cent were female. An average of 85% of the 18- to 89-year-old patients were considered to be healthy according to the ASA risk classification (P = 0.42). However, on applying the Munich risk checklist the average number of healthy individuals was 5% to 10% lower than that of the ASA risk classification.

[A profound stress reaction during epidural opiate analgesia in combination with weak neuroleptanalgesia in comparison with neuroleptanesthesia Type II alone]. / Profunde Stressreation unter epiduraler Opiatanalgesie in Kombination mit flacher Neuroleptanästhesie im Vergleich zur alleinigen Neuroleptanästhesie Typ II.

The modifying influence of anaesthetic procedures on stress reaction linked to operating trauma was observed by measurement of plasma concentration of beta-endorphin. In a prospective study 54 patients undergoing a radical gynaecological operation were allocated to either neuroleptanaesthesia type II or epidural morphine analgesia combined with slight neuroleptanaesthesia. The observation period was extended from the first preoperative day to the first postoperative day and included 11 measurements. The plasma concentration of beta-endorphin was determined by radioimmunoassay technique. At the beginning of the operation both groups of patients showed a significant increase in the plasma concentration of beta-endorphin, with the peak value occurring at the end of the operation. The patients undergoing epidural morphine analgesia in combination with slight neuroleptanaesthesia reached about five times higher levels of plasma concentration of beta-endorphin than the patients receiving neuroleptanaesthesia type II. The results show that the systemic administration of opiates suppresses the excessive activation of neuroendocrine stress systems to a greater extent than epidural administration. These results may be explained by the assumed worse quality of antinociception by epidural administration of morphine. This is thought to be caused by the late administration of the drug, by the non-selective occupation of the spinal opioid receptors and by the inadequate activation of the diffuse descending inhibitory control systems. The role of supraspinal mechanisms involved in opiate analgesia is discussed.

Magnitude and kinetics of alterations in plasma catecholamines and leukocyte beta-adrenergic receptors in response to anaesthesia and surgery.

We studied the response of the sympatho-adrenal system to varying intensities of different stimuli. Concentrations of norepinephrine and epinephrine in plasma as well as densities of beta 2-adrenergic receptors on mononuclear leukocytes were determined in patients subjected to operations of varying complexity and different types of anaesthesia. In patients undergoing hysterectomy (n = 9), the maximal increases in plasma norepinephrine and epinephrine were 2.7- and 2.8-fold, respectively, corresponding to a post-operative decrease of the mononuclear leukocyte beta 2-adrenergic receptors of 27% after 4 hours. Patients with coronary revascularization (n = 17) were randomly selected to receive either enflurane/N2O or neurolept anaesthesia. During intraoperative periods of stress, such as cardiopulmonary bypass and hypothermia, norepinephrine and epinephrine levels were 2-3 times higher in the neurolept patients, compared with the enflurane patients. In the former group, the respective maximal norepinephrine and epinephrine concentrations were 9.7 and 28 times the vasal values of the non-anaesthetized patients. One day postoperatively, the mononuclear leukocyte beta 2-receptor density decreased maximally by 45 +/- 11% in the enflurane patients, and by 53 +/- 6% in the neurolept patients. As early as two to five days after cardiac surgery, beta 2-receptor densities were no longer distinguishable from the preoperative values. Significant correlations between the increases in catecholamine concentrations and the decreases in beta 2-receptor densities did not exist. It is concluded that enflurane blocks the sympatho-adrenal response to surgical stress more effectively than neurolept anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive impairment after neuroleptanalgesia in cataract surgery.

This study was undertaken to evaluate the mental recovery of patients following cataract operations under neuroleptanalgesia. Mental function was assessed by Mini-Mental State (MMS) preoperatively and at 6 and 24 hours postoperatively. Preoperatively, 18.7% of the elderly had cognitive impairment of mental function while none in the younger group had any impairment (P less than 0.02). At six hours postoperatively, 29.7% of the elderly had cognitive impairment compared with 4% of the younger group (P less than 0.01). At 24 hours postoperatively, the percentage of elderly and younger patients with cognitive impairment had returned to preoperative levels. Baseline score and age were found to be significant predictors (P less than 0.004) of the 6-hour score and 24-hour score. In conclusion, cognitive impairment of mental function occurred in patients undergoing cataract operation with retrobulbar block and intravenous sedation at 6 hours postoperatively; MMS has the potential for use as a screening preoperative test for outpatients to identify those at risk for developing cognitive impairment.

[Importance of modulated neuroleptanalgesia in anterior chamber implantation]. / Intérêt de la neuroleptanalgésie modulée dans l'implantation de chambre antérieure.

About 192 anterior chamber implantations, the authors report the advantage to utilize modulated neuroleptanalgesia.

[The technic of sub-vigil anesthesia in plastic-reconstructive surgery]. / La tecnica di anestesia sub-vigile in chirurgia plastico-ricostruttiva.

The personal experience in plastic-reconstructive surgery with 395 cases of sub-vigil anaesthesia (neuroleptanalgesia + benzodiazepine in 124 patients (group A); ketamine + benzodiazepine in 138 patients (group B); neuroleptanalgesia + ketamine + benzodiazepine in 133 patients (group C) is described by the authors in the present study. They conclude that the sub-vigil anaesthesia is usually free from complications and a very safe, tolerable, expedient technique for plastic surgical procedures; furthermore, the result is good patient acceptance, a stable blood pressure and heart rate.