Diazepam-treated Patients Research Articles

OP.7A.06] TREATING HYPERTENSIVE CRISES BETWEEN GUIDELINES AND REAL-WORLD

Objective: Current ESH Guidelines are extensively devoted to diagnosis, management and follow-up of arterial hypertension in the “chronic” setting, whereas less attention is given to the acute management of hypertensive crises, a group of potentially life-threatening complications. Moreover, epidemiological data concerning hypertensive crises are limited. Design and method: During 2014, 457 consecutive patients with an initial systolic blood pressure (SBP) >170 mmHg and/or diastolic blood pressure (DBP) >110 mmHg were enrolled after being admitted to an Emergency Department (ED) serving a population of more than 50000 inhabitants, Results: Hypertensive crises represented 0.95% of the total number of ED admissions (n = 48054). Hypertensive emergencies (i.e. hypertensive crises associated with organ damage), were 113/457 (25%), the remaining 344/457 (75%) being hypertensive urgencies. Global mortality rate was 0.87%, (4% in the subset of hypertensive emergencies). Female patients were the majority in both hypertensive urgencies (65.1%) and emergencies (53.1%). Mean age was 68.5 years (range: 23–97). The presence of hypertension (either treated or untreated) was already known in 67.1% of cases. Treatment was associated with significant blood pressure reduction in both urgencies (SBP = −42.1 mmHg, DBP = −19.4 mmHg) and emergencies (SBP = −40.5 mmHg, DBP = −21 mmHg; p < 0.001 for both) in a relatively short time span (<5 hours). As expected, acute treatment of hypertensive emergencies was based on a combination of diuretics, nitrates, labetalol and urapidil. In contrast, in hypertensive urgencies the most commonly prescribed drugs were clonidine (44.3%) and diazepam (36.3%). Although not recognized as an antihypertensive drug, diazepam is widely used in the management of hypertensive crises. Notably, diazepam-treated patients achieved a similar extent of blood pressure reduction when compared with patients not receiving antianxiety treatment. Moreover, diazepam administration was associated with a faster reduction in blood pressure and a significantly lower number of associated anti-hypertensive drugs (0.7 vs 1.2; p < 0.01). During a 11-month follow-up, re-admissions caused by hypertensive crises were 63 (13.8%), without any difference related to diazepam treatment. Conclusions: Anti-anxiety drugs are commonly used in hypertensive crises, showing an interesting role in “real-world” treatment. Further studies are warranted to better define their role as “anti-hypertensive” drugs.

Impact of preoperative anxiolytic on surgical site infection in patients undergoing abdominal hysterectomy

An increased anxiety may be associated with a higher risk of surgical site infection (SSI), but there is little objective data on the effect of preoperative anxiolytic interventions on SSI. To address this issue, we evaluated the effects of preoperative diazepam on postoperative SSI following abdominal hysterectomy. This randomized, double-blinded, placebo-controlled study included 130 patients, American Society of Anesthesiologist physical status 1 or 2. Patients were randomly assigned to receive either oral diazepam 10 mg (n = 65) or placebo (n = 65) the night before and 1 hour prior to surgery. The assessment instruments were the Visual Analogue Scale and the State-Trait Anxiety Inventory. SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention with standard follow-up of 30 days. The relative risk (RR) was 1.79 (95% confidence interval [CI]: 1.31-2.43), and the number of patients that needed to be treated was 5.2 (95% CI: 2.74-50.76) to prevent 1 additional SSI. The RR for SSI in placebo-treated patients with high postoperative anxiety was 1.65 (95% CI: 1.07-2.56). Diazepam-treated patients showed lower postoperative anxiety and lower incidence of SSI up to 30 days after surgery compared with placebo in patients undergoing abdominal hysterectomy.

Paradoxical therapy in conversion reaction.

Paradoxical therapy consists of suggesting that the patient intentionally engages in the unwanted behaviour such as performing compulsive ritual or wanting a conversion attack. In this study, the subjects were selected by the emergency unit psychiatrist from patients who were admitted to the emergency unit with pseudoseizure. The diagnoses was based on DSM-IV criteria. Paradoxical intention was applied to half of the 30 patients with conversion disorders; the other half were treated with diazepam in order to examine the efficiency of the paradoxical intention versus diazepam. In both groups the differences of the anxiety scores at the beginning of the study were found to be insignificant (z=1.08, p=0.28). Of the 15 patients who completed paradoxical intention treatment, 14 (93.3%) responded favorably to paradoxical intention. On the other hand of 15 patients who completed diazepam therapy, 9 (60%) responded well to therapy and 6 patients carried on their conversion symptoms at the end of 6 weeks. Paradoxical intention-treated patients appeared to have greater improvements in anxiety scores (z=2.43, p<0.015) and conversion symptoms (t=2.27, p=0.034) than the diazepam-treated patients. The results of the present study are encouraging in that paradoxical intention can be effective in the treatment of conversion disorder.

Biochemical Assessment of Preoperative Stress

Diazepam 5 mg or an inert placebo tablet was given as preoperative hypnotic on the night before operation to two groups (n = 18 in each of healthy women having elective Caesarean section under spinal analgesia. A third group (n = 18) received no hypnotic. The quality of the preoperative night's sleep assessed subjectively was significantly better in the diazepam-treated patients compared with those receiving no drug. The diazepam-treated patients had also smaller CSF concentrations of noradrenaline (NA) and of the dopamine metabolite, 3, 4-dihydroxy phenylacetic acid (DOPAC). In comparison with the two other patient groups, in the diazepan group there was no correlation between demo-graphic, physiological or subjectively estimated variables and CSF or plasma measurements of monoamine transmitters and their metabolites. Preoperative fear and apprehension correlated most strongly with preoperative heart rate and with the increase in heart rate from the previous day. The monoamine neurotransmitters or their metabolites were of limited use in monitoring the intensity of preoperative fear and anxiety.

BIOCHEMICAL ASSESSMENT OF PREOPERATIVE STRESS: A STUDY WITH DIAZEPAM AND MEASUREMENT OF MONOAMINE METABOLITES AND CATECHOLAMINES IN CEREBROSPINAL FLUID AND PLASMA

Diazepam 5 mg or an inert placebo tablet was given as preoperative hypnotic on the night before operation to two groups (n = 18 in each) of healthy women having elective Caesarean section under spinal analgesia. A third group (n = 18) received no hypnotic. The quality of the preoperative night's sleep assessed subjectively was significantly better in the diazepam-treated patients compared with those receiving no drug. The diazepam-treated patients had also smaller CSF concentrations of noradrenaline (NA) and of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC). In comparison with the two other patient groups, in the diazepam group there was no correlation between demographic, physiological or subjectively estimated variables and CSF or plasma measurements of monoamine transmitters and their metabolites. Preoperative fear and apprehension correlated most strongly with preoperative heart rate and with the increase in heart rate from the previous day. The monoamine neurotransmitters or their metabolites were of limited use in monitoring the intensity of preoperative fear and anxiety.

Review of the side-effect profile of buspirone

In 984 patients with generalized anxiety disorder who received buspirone in double-blind studies, the incidence of drowsiness (9 percent) did not differ significantly from that (10 percent) reported in 334 patients who received placebo. A probability value of p ≤ 0.10 was the criterion for significance. The incidence of drowsiness in buspirone-treated patients was significantly less than that in each of the groups receiving diazepam (32 percent), clorazepate (26 percent), lorazepam (58 percent), or alprazolam (43 percent). The side effects that did occur significantly more frequently in the buspirone group than in the placebo group were dizziness (9 percent versus 2 percent), headache (7 percent versus 2 percent), nervousness (4 percent versus 1 percent), light-headedness (4 percent versus less than 1 percent), diarrhea (3 percent versus less than 1 percent), paresthesia (2 percent versus less than 1 percent), excitation (2 percent versus less than 1 percent), and sweating/clamminess (1 percent versus 0 percent). The severities of these effects were predominantly rated as only mild or moderate. Fatigue occurred less frequently in buspirone-treated patients than in those receiving any of the benzodiazepines, and weakness occurred more frequently in diazepam-treated patients. Depression occurred less frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or lorazepam. Impotence occurred only in clorazepate- and lorazepam-treated patients. Decreased libido occurred more frequently in diazepam-treated patients, whereas increased libido was more frequent in clorazepate-treated patients. Nausea was reported more frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or alprazolam; diarrhea occurred more frequently in the buspirone group than in the diazepam group. The mean daily doses of the various treatments were buspirone, 20 mg; diazepam, 20 mg; clorazepate, 24 mg; lorazepam, 3 mg; and alprazolam, 1.5 mg. In an open-field study in West Germany involving 5,414 patients, gastrointestinal-related complaints were the most frequently reported side effects.

The neuropharmacology of various diazepam antagonists

Recently, compounds which bind avidly to benzodiazepine binding sites have been shown to possess diazepam antagonist properties. For example, the benzodiazepine RO 15–1788 and the pyrazoloquinoline CGS 8216 can antagonize the anxiolytic, sedative, muscle relaxant and anticonvulsant properties of diazepam. The beta-carbolines have also been shown to antagonize several actions of diazepam. Other compounds inclucling physostigmine, naloxone, bicuculline, picrotoxin, caffeine and theophylline, lack appreciable affinity for benzodiazepine binding sites but do antagonize at least some of the behavioral actions of diazepam. Their antagonist properties are probably the result of opposing pharmacological actions rather than direct receptor antagonism. Clinically, a potent safe diazepam antagonist could be used to reverse effects of diazepam overdose and to speed recovery of diazepamtreated patients after various out-patient procedures.

Double-blind Study of Lorazepam and Diazepam in Status Epilepticus

Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted.

Double-blind study of lorazepam and diazepam in status epilepticus

Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted. (<i>JAMA</i>1983;249:1452-1454)

Hepatic cholesterol synthesis in man: effect of diazepam and other drugs.

The hepatic synthesis of cholesterol-measured as incorporation of 14C-acetate into digitonin-precipitable sterols-has been evaluated in needle biopsy material of normal untreated patients and patients under short-term treatment with Diazepam, Phenobarbital, Chlorpromazine or Diphenylhydantoin. A significant increase of cholesterol synthesis was observed in the first two groups with much higher levels of incorporation in the Diazepam-treated patients. Moreover in this group the levels were still elevated from 4 to 7 days after drug withdrawl. Ultrastructural and morphometric studies performed on the same biopsy material showed a significant increase of smooth endoplasmic reticulum in hepatocytes of Diazepam-treated patients; in addition, there seemed to be a positive correlation between the increased cholesterol synthesis and the formation of areas of non vesicular, type 2, smooth endoplasmic reticulum. These findings suggest an early stimulation of the liver cell microsomal system by Diazepam in man; they also point to side effects of some drugs, which are not predictable from studies in Wistar rats.

Diazepam as a Sedative in Induced Abortion

In 136 patients, who underwent induced abortion by the vacuum curettage method under local anaesthesia (paracervical block), the effect of 10 mg diazepam intravenously as preoperative sedative was investigated for its ability to abolish the subjective experience of pain. The trial was carried out as a paired sample, random, allocation, double-blind, fixed dose trial, and the statistical method was sequential analysis. Thirty-six pairs showed no difference and were excluded. After 32 pairs (24 A preferences and 8 O preferences), diazepam showed a significant superiority to placebo (p less than 0.05) (Fig. 1.) Amnesia for the procedure was reported by about one-quarter of the diazepam-treated patients, and in practically all cases the sedative effect had subsided 1-3 hours after the operation.

Diazepam as an Adjunct to Bronchoscopy

A controlled double-blind study of 50 patients undergoing bronchoscopy under topical anesthesia was done to determine the effectiveness of diazepam (Valium) premedication as compared to meperidine. The majority of the patients in both groups were able to relax and cooperate during the procedure. Cooperativeness was significantly better in the meperidine group. Anxiety and restlessness were affected similarly by the two drugs. Diazepam-treated patients were more often drowsy and confused than were the meperidine-treated patients. The procedure was easy to perform in over half the patients in both groups. Six (25 percent) of the diazepam-treated patients had no recall of the procedure 24 hours later as compared to two (8 percent) of the meperidine-treated patients. No serious complications related to either drug were noted. This study shows that diazepam as premedication for bronchoscopy is as effective as meperidine for producing relaxation and relieving anxiety but somewhat less effective for promoting cooperation. It can produce amnesia for the event in a significant number of patients. A controlled double-blind study of 50 patients undergoing bronchoscopy under topical anesthesia was done to determine the effectiveness of diazepam (Valium) premedication as compared to meperidine. The majority of the patients in both groups were able to relax and cooperate during the procedure. Cooperativeness was significantly better in the meperidine group. Anxiety and restlessness were affected similarly by the two drugs. Diazepam-treated patients were more often drowsy and confused than were the meperidine-treated patients. The procedure was easy to perform in over half the patients in both groups. Six (25 percent) of the diazepam-treated patients had no recall of the procedure 24 hours later as compared to two (8 percent) of the meperidine-treated patients. No serious complications related to either drug were noted. This study shows that diazepam as premedication for bronchoscopy is as effective as meperidine for producing relaxation and relieving anxiety but somewhat less effective for promoting cooperation. It can produce amnesia for the event in a significant number of patients.

Evaluation of diazepam (valium) in the symptomatic treatment of rheumatic disorders: A controlled comparative study

1. 1. Diazepam was compared with chlormezanone and carisoprodol in the symptomatic treatment of chronic rheumatic disorders. 2. 2. Sixty-five patients with active arthritis (rheumatoid, osteo-, or gouty), or fibrositis, received 2-week courses of each drug in random sequence, utilizing a double-blind cross-over technique. Administered in matching capsules, the average daily dosages amounted to 7.5 mg of diazepam, or 600 mg of chlormezanone, or 1050 mg of carisoprodol. 3. 3. Clinical response to each agent was measured by the relative degree of improvement in five symptoms—muscle spasm, pain, limitation of motion, anxiety and tension, and interference with daily activities—over the symptom severity present before each drug course. The differences in averaged symptom improvement scores (of each group of patients on each drug) represented the relative efficacy of each drug in relieving each symptom. 4. 4. Over-all results showed: 24 per cent of the diazepam-treated patients became symptom-free vs. 11 per cent on each of the two other drugs; in approximately 65 per cent of patients on each drug, moderate improvement was achieved, while only minimal improvement occurred in 11 per cent of those on diazepam vs. 24 per cent on each of the other drugs. Two patients, one on carisoprodol and one on chlormezanone, were unimproved. 5. 5. The differences in scored results between pairs of the 3 drugs, submitted to statistical analysis, indicated that diazepam effected significantly greater symptomatic improvement than did chlormezanone or carisoprodol. 6. 6. Side-effects occurred in 27 patients during diazepam therapy, in 38 on chlormezanone, and in 34 on carisoprodol; drowsiness was the most common side-reaction with each drug; none was of sufficient severity to discontinue medications.