Lorazepam in open-heart surgery--plasma concentrations before, during and after bypass following different dose regimens

Thirty-six patients (29 males and 7 females) undergoing open-heart surgery received one of three different dose regimens of lorazepam. All received a weight-related oral dose (2 mg, 3 mg or 4 mg) pre-operatively for night sedation. Twenty-four patients had an additional weight-related dose (2 mg, 3 mg or 4 mg intravenously) either as part of the induction (12 patients) or just prior to connection of the heat-lung machine (12 patients). Plasma concentrations of lorazepam were measured 20 minutes after induction, immediately before bypass, 30 and 60 on bypass and 30 minutes after bypass. Only when additional intravenous lorazepam was given prior to connection to the heart-lung machine were plasma lorazepam concentrations obtained compatible with complete amnesia.     

A double-blind comparison between nitrazepam, lorazepam, lormetazepam and placebo as preoperative night sedatives

Benzodiazepines are used as hypnotics to reduce anxiety and give a good night's sleep on the night prior to surgery. In a double-blind procedure, patients were given either lorazepam (2 mg or 4 mg), lormetazepam (1 mg or 2 mg), nitrazepam 10 mg or placebo. Measures were taken of sleep, anxiety, memory and after-effects. There was no evidence that the drugs reduced anxiety, nor evidence of amnesia. Quality and length of sleep was shown to be better for nitrazepam (P less than 0.05), lorazepam 2 mg (P less than 0.05) and lorazepam 4 mg (P less than 0.01), compared with placebo. However, significantly higher ratings of clumsiness and confusion as after-effects were found with nitrazepam (P less than 0.05), and clumsiness (P less than 0.005), slurred speech and blurred vision (P less than 0.01), sleepiness, nausea, weakness and confusion (P less than 0.05) with lorazepam 4 mg. It was concluded that lorazepam 2 mg produced the greatest net benefit.     

A double-blind comparison of the efficacy of lorazepam FDDF versus placebo for anesthesia premedication in children

Lorazepam was tried in a new formulation (FDDF) as premedication in twenty children, aged between 5-10 years. The study was performed in a double-blind fashion using lorazepam 1 mg and placebo in identical FDDF preparations. No significant differences were observed between the two treatment groups except for the recall of the venipuncture and awakening. Because of the lack of sedation observed the study was completed with an open trial on ten new subjects receiving 2 mg lorazepam FDDF. The quality of premedication was not found improved while more secretions were observed in the 2 mg lorazepam group. Recall of venipuncture and awakening was significantly less frequent in the 2 mg lorazepam group as compared to placebo. In both lorazepam groups awakening from anesthesia was prolonged. Side effects were reported in several patients receiving lorazepam. As lorazepam FDDF performed not better than a placebo as premedication for children its use is not recommended in pediatric anesthesia.     

COMPARATIVE STUDY OF TWO LONG-ACTING TRANQUILLIZERS FOR ORAL PREMEDICATION

Lorazepam 2.5 mg was compared with promethazine 50 mg as oralpremedication in a double-blind study in women. The premedicationwas given at the same time to all patients on each operatinglist, and both drugs continued to be effective 6 h after ingestion.A similar number of patients considered each drug to have relievedanxiety and the amnesic effect of lorazepam was confirmed. However,the use of lorazepam alone was accompanied by significantlymore salivation during and after anaesthesia than the use ofpromethazine, especially in patients in whom the trachea wasintubated. There was also a higher frequency of vomiting duringand after operation with lorazepam (seven of 67 patients) thanafter promethazine (one of 71 patients). Promethazine produceddyskinetic side-effects in six of 71 patients.     

COMPARISON OF THREE BENZODIAZEPINES FOR ORAL PREMEDICATION IN MINOR GYNAECOLOGICAL SURGERY

Diazepam 10 and 20 mg, lorazepam 2.5 and 5.0 mg, flunitrazepam1 and 2 mg, and a placebo, were compared in a randomized double-blindcontrolled trial pa oral premedication for 210 patients undergoingminor gymecological surgery. Flunitrazepam 1 mg and lorazepam2.5 mg were supaior to placebo (P<0.001 and P<0.05 respectively)in relieving patient anxiety whm asseased by a trained observer60 min after premedication. Flunitrazepam 1 mg also producedmore drowsfness (P<0.01) than the placebo. Camparisom ofother low-dose benzodiazepine groups with the placebo, and ofthe large dose with the small dose of each drug revealed nosignificant changes in anxiolysis or drowsiness. Dizziness andprolonged drowsiness were not apparent with low-dose flunitrazepam.The data suggests that flunitrazepam 1 mg offers advantagesover placebo, diazepam 10 mg and lorazepam 2.5 mg for routineoral pranedication in minor gynaecological surgery.     

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.     

LORAZEPAM AND MORPHINE FOR I.V. SURGICAL PREMEDICATION

The effects of i.v. lorazepam alone, in doses of 2 mg and 4mg, and combined with morphine 5 mg, were studied. Sedation,relief of anxiety, lack of recall, patient acceptance, physicianacceptance and side-effects were evaluated. The addition ofmorphine to lorazepam significantly improved sedation and reliefof anxiety. Physician acceptance and patient acceptance showedno significant difference between any of the combinations. Lackof recall was enhanced by increasing the dose of lorazepam from2 mg to 4 mg, independent of the addition of morphine. The onlysignificant side-effect was restlessness which occurred in 15%of patients receiving lorazepam 4 mg and 3% of patients receivinglorazepam 2 mg, again independent of the addition of morphine.     

Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia: Efficacy and Dose-Response Trials

Background: There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design.

Methods: The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0%vs. 25%vs. 50%vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale.

Results: Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03).     

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.     

Ventricular fluid pressure in neurosurgical patients receiving intravenous lorazepam for premedication

Summary The effect of 0.05 and 0.03 mg/kg of intravenously administered lorazepam on the ventricular fluid pressure (VFP) was recorded continuously for 45–90 minutes in 13 wakeful spontaneously breathing unanaesthetized patients with hydrocephalus. The initial VFP was low in 11 patients with low-pressure hydrocephalus, and at the upper level of normal in 2 who had stenosis of the aqueduct. Lorazepam caused minute changes in VFP. The largest transient increases (7 and 16 torr) occurred in the two patients with the highest initial VFP. Blood acid-base balance, blood pressure, and heart rate remained unaltered. However, lorazepam caused such drowsiness that it was difficult to check the patients' level of consciousness. For this reason, intravenously administered lorazepam in a dosage of 0.03 mg/kg or more seems unsuitable for premedication in neurosurgical patients with brain disease.     

Clinical trial with lorazepam in pre-operative anxiety.

An important part of the pre-operative preparation of a patient consists in the treatment of his anxiety. One hundred eighty-two patients (varying in age from 17 to 80 years) were sedated for surgery with lorazepam. The evening before intervention, each patient received 1 tablet of lorazepam (2.5 mg) and on the day of operation (90 minutes before induction of the anesthesia), each patient received an I.M. injection of lorazepam and atropine, the dosage being adjusted to body weight. The prior administration of lorazepam usually gives very good results with only slight risk of side-effects and without unhappy recollections of the pre- and post-operative periods. Most of the patients were very calm, being well rested, conscious and capable of conversation. In our experience the sedation of anxious patients with lorazepam would seem to be a very good and safe procedure.     

EFFECT OF ORAL BENZODIAZEPINES ON MEMORY

The effects of the oral administration of diazepam 5, 10 and20 mg, flunitrazcpam 0.5 and 1 mg and lorazepam 1,2 and 4 mgon memory were studied in groups of healthy patients beforesurgery. The degree of sedation was noted also. A dose-relatedamnesic effect was produced by all the drugs, but this was notsignificant with diazepam 5 mg and lorazepam 1 mg. Larger dosesof diazepam (10 and 20 mg) produced brief amnesia comparableto equivalent doses of flunitrazepam (0.5 and 1 mg). There wasthe same delay in the onset of amnesia after oral lorazepam4 mg as when it was given i.v. and its effect lasted for atleast 90 min after administration. In contrast to the effectof the same drugs given i.v., drowsiness and failure of recognitionfollow a similar time course.     

Anxiolysis and postoperative pain in patients undergoing spinal anesthesia for abdominal hysterectomy

AIM: The relationship between pain and psychological factors is well known. The aim of the study was to evaluate the influence of lorazepam, given before total abdominal hysterectomy, on postoperative pain control. METHODS: Sixty patients, enrolled in the study, were defined as either anxious or not anxious when the State/Trait Anxiety Inventory (STAI) score was =/>51 or =/< 50, respectively. The anxious patients were randomly assigned to receive oral lorazepam 0.035 mg/kg the night and 2 h before surgery (Group A), or placebo at the same time (Group B). The not anxious patients were assigned to receive oral lorazepam 0.035 mg/kg the night and 2 h before surgery (Group C), or placebo at the same time (Group D). Anesthesia was performed with subarachnoidal block. Ketorolac was used for postoperative pain. As rescue drug, tramadol was administered using a patient controlled analgesia (PCA) modality. Postoperative pain was assessed during the 24 h after surgery by tramadol consumption. RESULTS: Tramadol consumption was significantly greater in Group B (216.3+/-58.9 mg) than in Groups A, C and D respectively (150.9+/-28.9 mg; 153.6+/-39.9 mg; 154.4+/-39.9 mg). Group B showed a significantly higher pain score compared to the other groups during the first 8 h. No difference in patient satisfaction with perioperative treatment was noted. CONCLUSION: Preoperative lorazepam reduced perioperative anxiety. This could explain the better postoperative pain control in patients undergoing hysterectomy, a very stressful surgical procedure.     

Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials

BACKGROUND: There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design. METHODS: The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale. RESULTS: Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03). CONCLUSIONS: Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted.     

Lorazepam as a premedicant for day-case surgery: an assessment

The sedative effect of 2 mg of lorazepam was assessed in eleven patients undergoing minor "day case" surgery and the results compared with a control group of eleven patients receiving a placebo. Sedation was assessed by a scoring method and quantified in terms of change in plasma cortisol levels. The results indicate that 2 mg of oral lorazepam produces good sedation (superior to nitrazepam in terms of plasma cortisol reduction) and has a postoperative anti-emetic effect but its prolonged duration of action makes it unsuitable for patients returning home within 8 hours of premedication.     

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.     

Bromazepam as oral premedication. A comparison with lorazepam

A double-blind trial of bromazepam 6 mg versus lorazepam 2 mg as oral premedicant agents was undertaken. A total of 153 patients were studied; 78 received bromazepam and 75 lorazepam. Objective and subjective assessments of sedation, amnesia, nausea and vomiting were performed. No significant difference between the two groups was found. It was concluded that bromazepam 6 mg and lorazepam 2 mg were equally satisfactory as premedicant drugs.     

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.     

Lorazepam and diazepam as adjuncts to epidural anaesthesia for caesarean section

Lorazepam 0.05 mg X kg-1 and diazepam 0.1 mg X kg-1 administered intravenously were compared as sedatives for 42 patients undergoing Caesarean Section under epidural anaesthesia. After receiving the drug, 15 per cent of the diazepam patients and 32 per cent of the lorazepam patients were still agitated. Ten per cent of the diazepam patients and 36 per cent of the lorazepam patients had severe symptoms of delirium. These included hallucinations, confusion, agitation, restlessness, inappropriate weeping and repetitive hand movements. Memory impairment was greater with lorazepam. Thirty-five per cent of the diazepam patients had pain at the injection site. None of the lorazepam patients had such pain. Respiratory rate, heart rate and mean blood pressure did not change significantly in either group. Half the patients who had been given lorazepam had side effects that were bothersome enough to cause them to complain the following day. Lorazepam and diazepam were both unsatisfactory as sedatives for patients having Caesarean Section.     

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.