Unpredictable Central Nervous System Effects after Lorazepam Premedication for Neurosurgery

Administration of lorazepam for preanaesthetic medication is generally expected to produce amnesic action. We conducted two studies to evaluate the relationship of plasma levels of lorazepam with its clinical effects. Forty patients, receiving 0.03 or 0.05 mg/kg lorazepam i.m. as preanaesthetic medication for variolis neurosurgical procedures, were asked 24 h after anaesthesia whether they could recall the insertion of the i.v. needle and a picture shown to them before induction of anaesthesia. Another 11 patients were given 0.03 mg/kg lorazepam i.v. and their degree of drowsiness was rated immediately before induction of anaesthesia. Plasma levels of lorazepam were measured by gaschromatography from samples drawn before induction of anaesthesia. No relationship between either the dose of lorazepam used or the plasma levels of lorazepam and the incidence of amnesia or the degree of drowsiness was observed. Three patients receiving 0.05 mg/kg of lorazepam i.m. had prolonged drowsiness, which made it diflicult to check the patients' neurological condition after the operation, It is postulated that the unpredictable and variable central nervous system effects of lorazepam in neurosurgical patients may be due to differences in the capacity of lorazepam to penetrate the blood brain barrier.     

Failure of Intramuscularly Administered Lorazepam and Scopolamine-Morphine Premedication to Produce Amnesic Effects to Supplement Conduction Anaesthesia

Patients undergoing surgery under regional anaesthesia often prefer to be sedated and do not later want to recall the procedure. One hundred and twenty-one patients scheduled for various surgical procedures under epidural, spinal, sacral, or brachial plexus blockades received 1 mg/kg of pethidine, 0.007 mg/kg of scopolamine, plus 0.14 mg/kg of morphine, or 0.03 mg/kg or 0.06 mg/kg or lorazepam intramuscularly as preanaesthetic medication before the operation. The patients's self-assessments of degree of fatigue and apprehension were similar after each premedication when assessed before operation. Postoperative anxiety and confusion as well as need for postoperative care and supervision were greatest after 0.06mg/kg of lorazepam. Significantly (P smaller than 0.05 to P smaller than 0.01) fewer patients given 0.06 mg/kg or lorazepam remembered different events and procedures carried out on them before and after operation than those given other premedications, but no significant differences were noted in patients' ability to recall the performance of operation when asked on the following day. Seventy-seven, 63, and 57% of patients receiving 0.06 mg/kg of lorazepam remembered the start of blockade, performance of operation, and stay in recovery room, respectively. Intravenous sedation should be preferred to these intramuscularly administered premedications if drug-induced amnesia is sought to supplement local anaesthetic techniques.     

The Influence of Intramuscularly Administered Pethidine on the Amnesic Effects of Intravenous Diazepam during Intravenous Regional Anaesthesia

Patients undergoing surgery under regional anaesthesia often receive narcotic analgesics for premedication which may modify the sedative and amnesic effects of intravenously administered diazepam. Sixty-two patients scheduled for upper extremity surgery under intravenous regional anaesthesia received 0.15 mg/kg of diazepam intravenously to supplement the local anaesthesia. Thirty-two of the patients received 0.01 mg/kg of atropine plus 1 mg/kg of pethidine and 30 patients only atropine intramuscularly approximately 1 h before the injection of diazepam. Another 30 patients received the same atropine-pethidine premedication and saline intravenously, and served as a reference group. Atropine-pethidine premedication followed by saline did not produce any amnesic effects. Sixty-nine and 38% of patients receiving atropine-pethidine premedication followed by diazepam did not remember a picture shown to them 15 min after diazepam injection or the performance of operation, respectively, the respective figures for patients given atropine premedication followed by diazepam being only 23% and 0% (P<0.01 - 0.001 between groups). The anti-recall of painful stimulus (exanguination) was significantly (P<0.01) more common when diazepam was given after pethidine premedication (31%) when compared to its injection after atropine alone (7 %). The drowsiness produced by the drugs was greatest and the overall patient acceptability of the technique used most satisfactory when pethidine was used for premedication and diazepam for sedation. It is concluded that intramuscularly administered pethidine potentiates the amnesic action of intravenous diazepam for painful stimuli, prolongs the amnesic action of diazepam for visual stimuli and improves the patients' acceptability of intravenous regional anaesthesia supplemented by intravenous diazepam.     

Buprenorphine as premedication and as analgesic during and after light isoflurane-N2O-O2 anaesthesia. A comparison with oxycodone plus fentanyl

Sixty patients undergoing gynaecological laparotomies under isoflurane anaesthesia received 0.4 mg of buprenorphine sublingually or 0.12 mg/kg of oxycodone intramuscularly in random order for preanaesthetic medication. Patients premedicated with buprenorphine were given buprenorphine before, during and after anaesthesia and patients premedicated with oxycodone received fentanyl before and during anaesthesia and oxycodone after anaesthesia. Buprenorphine premedication produced less drowsiness and sedation and alleviated patients' apprehension significantly (P less than 0.05) less than oxycodone. Systolic and diastolic blood pressure and heart rate were significantly (P less than 0.05 to P less than 0.01) higher after intubation in the buprenorphine group when compared with the oxycodone plus fentanyl group. After anaesthesia, spontaneous respiration started rapidly; the return of consciousness and immediate recovery occurred at the same rate in both groups. In the recovery room moderate to severe pain was more common (P less than 0.05) in the oxycodone plus fentanyl group than in the buprenorphine group. The respiratory rate in the recovery room was lower among patients given buprenorphine, and two patients given buprenorphine developed severe respiratory depression. In the ward (2 to 24 h after operation) sublingual buprenorphine provided pain relief as good as intramuscularly administered oxycodone. No differences were noted in the incidence or severity of emetic symptoms between the groups. It is concluded that buprenorphine can provide good postoperative pain relief for gynaecological laparotomies performed under light isoflurane anaesthesia, but patients need to be monitored carefully after operation because of the possibility of respiratory depression.     

Cardiovascular and respiratory effects of oral premedication with trimeprazine and droperidol in children

The systolic blood pressure, pulse rate and respiratory rate were assessed in 112 children before and after receiving premedication consisting of trimeprazine (3 mg/kg) and droperidol (0.2 mg/kg) by mouth. A mild (10%) drop in blood pressure was shown, but no statistical difference was found in the other parameters measured. The premedication is highly efficacious, 70% of patients being asleep in the preanaesthetic room; 27% were calm and only 3% were distressed or crying.     

Lorazepam as a premedicant in dental surgery

In a double-blind study, 100 young, healthy (American Society of Anesthesiologists physical status 1) patients received lorazepam (Ativan; Wyeth) 2,5 mg or placebo orally as premedication before general anaesthesia for extraction of wisdom teeth. Lorazepam produced a significant reduction in the incidence of pre-operative anxiety and post-anaesthetic headache compared with placebo (P less than 0,01). Anterograde amnesia was also more frequent in the patients who had received lorazepam (P less than 0.001). The medicolegal implications of using lorazepam as a premedicant in dental surgery at a day clinic are discussed.     

Diclofenac premedication but not intra-articular ropivacaine alleviates pain following day-case knee arthroscopy

PURPOSE: To compare the postoperative analgesic effects of 50 mg diclofenac p.o. before surgery and intra-articular ropivacaine injected after diagnostic day-case knee arthroscopy performed under spinal anesthesia. METHODS: In a randomized, double-blind investigation, 200 ASA physical status 1-2 outpatients, age 18-60 yr, received either 50 mg diclofenac p.o. or placebo one hour before operation (100 patients per group), and intraarticular injections of either 20 ml of ropivacaine 0.5% or 20 ml of saline 0.9% (50 patients in each premedication groups). Patients received 50 mg diclofenac p.o. prn and, if needed, 0.1 mg x kg(-1) oxycodone im for postoperative pain relief. Patients were discharged home with a supply of 50 mg diclofenac tablets and were given a sheet of paper with knee pain VAS scales and a questionnaire of analgesics taken. Patients rated their VAS scores eight hours after surgery and in the moming and at the end of the first and the second postoperative days, respectively. RESULTS: The only statistically significant difference was found when the diclofenac groups were combined and compared with the combined placebo premedication groups. The VAS scores of knee pain at eight hours after the operation were 19+/-22 in the two diclofenac premedication groups and 32+/-28 in the two placebo groups (P = 0.001). CONCLUSIONS: Diclofenac premedication p.o. reduced the VAS scores at eight hours postoperatively while intra-articular ropivacaine did not.     

A comparative study of the efficacy and tolerance of dipotassium clorazepate and flunitrazepam for oral premedication]

The literature shows that benzodiazepines, in view of their anxiolytic, sedative, amnesic, muscle relaxant and anticonvulsive action, are the most important substances for premedication. Eminent workers regard anxiolysis as the most important aim of premedication. In the present clinical study, oral administration of the two different benzodiazepine derivatives, flunitrazepam (F) and chlorazepate dipotassium (CD) have been explored with a view to side effects, tolerance, quality of sleep during the night, anxiolytic effect and sedation. The study involved 108 women patients aged from 20 to 60 years (ASA class I or II), all scheduled to undergo gynecological surgery in general anesthesia. There were also 20 women who received no premedication. The three groups of patients were further divided into early (operation started before 10:30 a.m.) and late-operation (operation started after 10:30 a.m.) groups. The test drugs were administered as follows: 43 women received 50 mg CD p.o. on the evening before the operation, followed by 25 mg p.o. in the morning; 45 women received 2 mg F p.o. on the evening before the operation, followed by 1 mg p.o. in the morning. All patients took the preoperative premedication at 7 o'clock in the morning. Following this medication, the anxiolytic, sedative, and amnesic effects, side effects, vigilance and O2 saturation (SaO2) were determined at defined points during the day of the operation and the 1st postoperative day. Blood pressure and heart rate were recorded and interpreted as physiological stress parameters. Anxiolysis was determined using the Erlangen Anxiety Scale (EAS) of Galster and Sp?rl; the degree of sedation was assessed by the anesthesiologist; amnesia was determined by the patients' recognition of picture cards; vigilance and side-effects were assessed by standardized questionnaires. Both active drugs clearly improved the quality of sleep in the night before the operation over that experienced with no premedication. There were no significant differences among the three groups in the physiological stress parameters. The preoperative SaO2 saturation was decreased significantly by oral F, but it was always more than 95%. CD had little influence on the SaO2. Unwanted somatic symptoms were found a little more frequently in the group without any premedication. There were no signs of restricted tolerance for either of the test drugs. In the premedicated groups, pre- and postoperative anxiety decreased significantly.(ABSTRACT TRUNCATED AT 400 WORDS)     

PREMEDICATION WITH LORAZEPAM FOR BRONCHOSCOPY UNDER GENERAL ANAESTHESIA

Lorazepam 3 or 4 mg i.m. was given to 100 patients as premedicationbefore bronchoscopy under thiopentone-suxamethonium anaesthesia.Forty-nine of the patients assessed as anxious received orallorazepam as preoperative night sedation also. Lorazepam wasan effective night sedative. Forty-two of the 49 patients sleptwell and were calm and co-operative in the morning. Followingthe i.m. injection of lorazepam, 64% of patients had completelack of recall for 4–10 h following premedication. Only5% recalled correctly a simple objective test of memory initiatedin the anaesthetic room. The frequency of recall was higherin those who consumed alcohol regularly and in females. Therewas one case of awareness during bronchoscopy in a patient whoreceived only a small dose of lorazepam (2.8 mg per 70 kg).Side-effects were minimal and patient acceptance was impressive.These results show an advance on previous studies using pethidineand diazepam. Further improvement is needed, particularly inadjusting the dose of lorazepam to body weight and to factorssuch as age, sex and alcohol intake.     

Effects of different doses of oral ketamine for premedication of children

BACKGROUND AND OBJECTIVE: A need exists for a safe and effective oral preanaesthetic medication for use in children undergoing elective surgery. The study sought to define the dose of oral ketamine that would facilitate induction of anaesthesia without causing significant side-effects. METHODS: We studied 80 children undergoing elective surgery under general anaesthesia who received oral ketamine 4, 6 or 8 mg kg(-1) in a prospective, randomized, double-blind placebo controlled study. We compared the reaction to separation from parents, transport to the operating room, the response to intravenous cannula insertion and application of an anaesthetic facemask, the induction of anaesthesia and recovery from anaesthesia. RESULTS: In the group receiving ketamine 8 mg kg(-1), the children were significantly calmer than those of the other groups, and anaesthesia induction was more comfortable. Recovery from anaesthesia was longer in the group receiving ketamine 8 mg kg(-1) compared with the other groups, but no differences between the groups were observed after 2 h in the recovery room. CONCLUSIONS: It is concluded that oral ketamine 8 mg kg(-1) is an effective oral premedication in inpatient children undergoing elective surgery.     

The effects of cimetidine and ranitidine with and without metoclopramide on gastric volume and pH in morbidly obese patients

The efficacy of preanaesthetic intravenous cimetidine versus ranitidine with and without metoclopramide for acid aspiration prophylaxis was assessed in 60 morbidly obese patients in a double-blind manner. Group 1 patients received cimetidine 300 mg + saline. Group 2 patients received cimetidine 300 mg + metoclopramide 10 mg. Group 3 patients received ranitidine 100 mg + saline. Group 4 patients received ranitidine 100 mg + metoclopramide 10 mg. Gastric fluid was aspirated for analysis of volume and pH following induction of anaesthesia. All four premedication regimens were equally effective in reducing the gastric volume and acidity and the inclusion of metoclopramide had no additive effect. Although statistically not significant, two patients in the cimetidine groups remained at risk (volume greater than 25 ml and pH less than 2.5) while no patients in the ranitidine groups remained so.     

Lorazepam as night sedation and premedication: a comparison with diazepam

Fifty healthy female patients scheduled for surgery were randonly allocated into two groups in a double-blind study. One group received lorazepam 2.5 mg orally at 2200 h on the evening before surgery as night sedation, and again at 0800 h on the morning before surgery as premedication. The second group received diazepam 10 mg orally at the samte times. The quality of sleep the night before surgery was superior in the lorazepam group (p less than 0.02). The frequency of effective sedation produced pre-operatively was similar in both groups. Although the incidence of amnesia for visual stimuli following lorazapam was higher (p less than 0.05) than with diazepam, there was no difference in the recall of auditory and painful stimuli. The overall incidence of side effects was similar for each drug and at the dosage used no difference was found in the time to awaken from anaesthesia.     

A comparison of two different doses of ketamine with midazolam and midazolam alone as oral preanaesthetic medication on recovery after sevoflurane anaesthesia in children

BACKGROUND: This investigation prospectively evaluated the effect of oral premedication of two different doses of ketamine with midazolam and midazolam alone on the recovery of children after sevoflurane anaesthesia. METHODS: In a randomized, double-blind study, 79 children (aged 1-8 years, ASA physical status I or II) were assigned to receive one of three premedications in a volume of 0.5 ml x kg(-1): group 1 received midazolam 0.5 mg x kg(-1) (MD); group 2 received midazolam 0.5 mg x kg(-1) with ketamine 1.8 mg x kg(-1) (MK-1); and group 3 received midazolam 0.5 mg x kg(-1) with ketamine 3 mg x kg(-1) (MK-2). The reactions of the children during administration were noted. Anaesthesia was induced by facemask with incremental sevoflurane administration. All children received alfentanil (15 micro g x kg(-1)). Tracheal intubation was facilitated by mivacurium (0.2 mg x kg(-1)). Anaesthesia was maintained with sevoflurane and an additional dose of alfentanil, if necessary. During recovery, the time interval between discontinuation of anaesthesia and arousal (spontaneous ventilation, extubation) were recorded. RESULTS: Emergence (spontaneous ventilation, extubation) and recovery times (discharge, Aldrete score=9) did not differ significantly between groups (P=0.24, P=0.59 and P=0.145, respectively). CONCLUSIONS: The combination of midazolam and ketamine as oral preanaesthetic medication did not significantly affect the recovery time of children after sevoflurane anaesthesia.     

Comparison of methohexital and pentobarbital for premedication in children

Thirty children scheduled for elective orchiopexy or herniotomy were consecutively assigned at random to premedication with methohexital 80 mg/ml, 20 mg/kg rectally, 15 min before transportation to the operating room, or pentobarbital 28 mg/ml, 7 mg/kg rectally, 45 min before transportation. The quality of premedication was recorded at induction with halothane 1-2% and 60% N2O in O2 by mask. All patients received a caudal injection of bupivacaine 1.9 mg/ml, 1.25 ml/kg before surgery. Following completion of anaesthesia, the postoperative wake-up time and the duration of stay in the post-operative recovery room were recorded. The degree and quality of recovery were assessed using the Aldrete score every 30 min until discharge from the recovery room. The group of children receiving methohexital showed a highly significantly shorter awakening time, and a highly significantly shorter stay in the recovery room compared to the pentobarbital group. The children in both groups had a quiet, easy recovery without significant signs of confusion or agitation, and no difference in quality of recovery could be shown. Emergence delirium or agitation in connection with pentobarbital premedication and a possible relation to postoperative pain is discussed.     

Triazolam premedication

A randomised, double blind study, of 58 female patients undergoing laparoscopic investigation was carried out to compare triazolam 0.25 mg, lorazepam 2 mg, or placebo as oral premedication. Each patient was assessed by only one of the authors both pre- and postoperatively with regard to anxiolysis, sedation and rapidity of recovery. Triazolam and lorazepam were each associated with a significant reduction in anxiety compared to the initial assessment, whereas placebo had no anxiolytic effect. Sixty minutes after premedication, patients who had received triazolam were significantly more sleepy than patients given placebo or lorazepam. Two hours after the operation, the patients who had had triazolam or lorazepam were significantly more sleepy than those who received placebo. However, at 6 hours postoperatively there was no difference between triazolam and placebo, whilst those who had been given lorazepam were still significantly more sleepy than those given placebo. Triazolam appears to offer advantages over either lorazepam or placebo in patients who require rapid recovery, sedation and reduction in pre-operative anxiety.     

Preoperative infusion of amino acids prevents postoperative hypothermia

Intraoperative infusion of amino acids has been found to stimulate energy expenditure and thereby prevent anaesthesia-induced hypothermia. Rectal temperature and respiratory gas exchange were measured in 24 female patients before and after isoflurane anaesthesia. Sixteen patients had an amino acid mixture of 240 kJ h-1, infused over 1-2 h before anaesthesia and eight control patients received saline. We compared the results with data from six female volunteers treated with amino acids; they were not premedicated or anaesthetized. In lorazepam premedicated patients, amino acids increased the pre-anaesthesia temperature by 0.3 degrees C h-1, twice that observed in the volunteers. At awakening after anaesthesia, energy expenditure increased to 50-60% above baseline in the amino acid treated patients, while in the control patients, receiving saline, no increase occurred, despite vigorous shivering. Amino acid infusion prevented hypothermia by increasing heat accumulation and causing delayed stimulation of heat production. The heat accumulation response to amino acid infusion was increased after premedication with lorazepam.      

Oxycodone and ketobemidone for oral premedication

In a prospective, randomised and double-blinded study the preoperative sedative effect and the postoperative use of analgesics were compared in 90 patients undergoing inguinal hernia repair under general anaesthesia, premedicated orally with ketobemidone 10 mg, sustained-release oxycodone 10 mg or placebo. All patients had a local infiltration with bupivacaine after wound closure. Oral paracetamol 1 g×4 and dextropropoyphene 100 mg×4 were given postoperatively and iv ketobemidone was added if the pain score was >3 on a visual analogue scale from 0 to 10. Oxycodone, ketobemidone and placebo had a similar sedative effect before surgery. The use of ketobemidone after surgery was reduced by 40% in the oxycodone group compared to placebo (P<0.05). No reduction was noted in the ketobemidone group. Conclusion: Sustained-release oxycodone—but not ketobemidone—for oral premedication reduced the postoperative use of opioids after surgery.     

The use of lorazepam as a soporific and for premedication.

An open study, in which 48 patients scheduled for elective surgery received either 1,25 mg or 2,5 mg of lorazepam (orally) as a soporific the night before surgery and as premedication immediately prior to surgery, revealed that lorazepam produced a good night's rest and a desirable calm immediately prior to surgery. Vital signs remained stable throughout the operative procedure, and vomiting and other reactions were virtually absent.     

EFFECT OF SALBUTAMOL AND SUXAMETHONIUM ON THE PLASMA POTASSIUM CONCENTRATION

In a double-blind randomized study, patients received premedicationwith Iorazepam 0.04 mg kg–^–1 and salbutamol 0.1mg kg–^–1 or lorazepam 0.04 mg kg–^–1and placebo given orally 2.5–3 h before anaesthesia. Theplasma potassium concentration was measured at the time of premedication,before the induction of anaesthesia and at selected intervalsafter suxa-methonium 1 mg kg–^–1 i. v. The plasmapotassium concentration was lower in those patients who receivedsalbutamol than in those given placebo, and remained lower atall the subsequent sample times. Oral salbutamol did not appearto affect the incidence of suxamethonium related muscle pain.     

Sublingual triazolam versus peroral diazepam as a premedication for general anaesthesia

Sublingual triazolam 0.2 mg (T) was compared with peroral diazepam 10 mg (D) as a premedicant in a randomised, doubleblind study. Eighty-one ASA I-III patients aged 18– 70 yr, scheduled for elective surgery and general anaesthesia were studied. The patients were premedicated about one hour preoperatively. The T-group subjects (n = 41) received triazolam sl after a placebo po and the D-group subjects (n = 40) diazepam po before a sl placebo. Anxiety and sedation were evaluated before premedication, every 15 min after that until the patient was removed to the operating room, just before the induction of anaesthesia and both 30 and 60 min after operation. Anxiety and sedation were evaluated by the patient using a visual analogue scale (VAS) and by the anaesthetist with a scale of 0– 3 for anxiety and 0– 4 for sedation. The patients’ experiences with regards to their premedication and visit to the operating unit were investigated after the operation. In both groups sedation and anxiolysis became different at 30– 45 min after premedication, but at the time just before the induction of anaesthesia there was sedation and anxiolysis only in the T-group. There was no difference between the groups at any time. The T-group patients were more satisfied with their premedication and visit to the operating unit. The study drugs did not cause any cardiorespiratory or other side effects. We conclude that triazolam 0.2 mg sl is at least as effective a premedication as diazepam 10 mg po, that it is suitable for patients that cannot swallow, and that the patients were more satisfied with it than with diazepam.