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PubMed2003

Intrathecal midazolam added to bupivacaine improves the duration and quality of spinal anaesthesia.

BACKGROUND: The antinociceptive action of intrathecal midazolam is well documented. In this prospective study, we investigated the addition of midazolam to intrathecal bupivacaine on the duration and quality of spinal blockade. METHODS: Forty ASA I or II adult patients undergoing lower abdominal surgery were selected for the study. The patients were randomly allocated to receive 3 ml of 0.5% hyperbaric bupivacaine intrathecally either alone or with 1 mg of midazolam using a combined spinal epidural technique. The duration and quality of sensory and motor block, perioperative analgesia, haemodynamic changes, and sedation levels were assessed. RESULTS: The duration of sensory block (i.e. time to regression to the S2 segment) was significantly longer in the midazolam group than the control group (218 min vs. 165 min; P < 0.001). The duration of motor block was also prolonged in the midazolam group as compared with the control group (P < 0.01). In 90% of the patients in the midazolam group, the quality of block was adequate during the intra-operative period as compared with only 65% of the patients in the control group (P < 0.05). The duration of effective analgesia was longer in the midazolam group than in the control group (199 vs. 103 min; P < 0.001). Blood pressure, heart rate, oxygen saturation and sedation scores were comparable in both groups. No neurological deficit or other significant adverse effects were recorded. CONCLUSION: The addition of intrathecal midazolam to bupivacaine significantly improves the duration and quality of spinal anaesthesia and provides prolonged perioperative analgesia without significant side-effects.

Adult↗
PubMed1992

Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers.

The pharmacodynamics of midazolam and its main metabolite alpha-hydroxymidazolam were characterized in individual subjects by use of saccadic eye movement and electroencephalographic (EEG) effect measurements. Eight healthy volunteers received 0.1 mg/kg midazolam intravenously in 15 minutes, 0.15 mg/kg alpha-hydroxymidazolam intravenously in 15 minutes, 7.5 mg midazolam orally and placebo in a randomized, double-blind, four-way crossover experiment. Plasma concentrations of midazolam, alpha-hydroxymidazolam and 4-hydroxymidazolam were measured by gas chromatography. The amplitudes in the 11.5 to 30 Hz (beta) frequency band were used as EEG effect measure. The concentration-effect relationships were quantified by the sigmoid maximum effect model. The median effective concentrations of midazolam and alpha-hydroxymidazolam were (mean +/- SE) 77 +/- 15 and 98 +/- 17 ng/ml, respectively, for the EEG effect measure. For peak saccadic velocity the values were 40 +/- 7 ng/ml for midazolam and 49 +/- 10 ng/ml for alpha-hydroxymidazolam. The maximum effect values were similar for both compounds. The effects observed after oral administration of midazolam could not be predicted accurately by an additive and competitive interaction model. It seems that alpha-hydroxymidazolam is highly potent with respect to the measured effects and contributes significantly to those effects of midazolam after oral administration.

Administration, Oral↗
PubMed2002

A study of the effectiveness of oral midazolam sedation for orthodontic extraction of permanent teeth in children: a prospective, randomised, controlled, crossover trial.

OBJECTIVES: To assess the safety, effectiveness and acceptability of o:ral midazolam sedation for orthodontic extraction of permanent teeth in children. DESIGN: A prospective, randomised, controlled, crossover trial. METHODS: A total of 26 children aged 10-16 (ASA I), referred for orthodontic extraction of premolar or canine teeth under sedation, were included in the study. Each child required two treatment sessions for the extraction of equivalent teeth on opposite sides of the mouth. Each subject was sedated with either ora midazolam (0.5 mg/kg) or nitrous oxide and oxygen (30%/70%) at the first visit and the alternative form at the second visit. At each visit two teeth were extracted, one upper and one lower. Heart rate, arterial oxygen saturation, respiration rate, sedation and behavioural scores were recorded every five minutes. Overall behaviour, patient acceptance and patient satisfaction were recorded at the end of treatment. RESULTS: Of the 26 children included in the study there were 12 males and 14 females. The mean age was 12.5 years. The mean heart rate and respiratory rate for both groups were similar and within acceptable clinical limits. The lowest mean arterial oxygen saturation levels for nitrous oxide and midazolam sedation were 97.7% and 95.0% respectively. Although midazolam caused greater oxygen desaturation, the range (91%-100%) was within safe limits for conscious sedation. The mean level of sedation was greater in the midazolam group compared with the nitrous oxide group and all but one case completed treatment. A total of 23 patients (88%) said they would be prepared to have ora midazolam sedation again and 17 (65%) actually preferred oral midazolam to nitrous oxide sedation. CONCLUSION: Oral midazolam (0.5mg/kg) appears to be a safe and acceptable form of sedation for 10-16 year old paediatric dental patients.

Administration, Oral↗
PubMed1997

Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.

AIMS: This study aimed to investigate the pharmacodynamics and pharmacokinetics of ascending doses of Ro 48-8684, compared with midazolam, in healthy subjects during first administration to man. METHODS: The study was double-blind and five-way crossover (three ascending doses, placebo, fixed midazolam dose), performed in two groups of five males. Ro 48-8684 was infused in doses of 0.1-0.3-1 mg in the first group, and 1-3-10 mg in the second, with different infusion rates (expressed as mg min(-1)) among doses. Midazolam was infused at 0.1 mg(-1) kg. Infusions were stopped after 20 min or if sedation became too strong for proper performance of saccadic eye movements. Pharmacokinetics and pharmacodynamics and their relationships were evaluated as described in the companion article. RESULTS: Ro 48-8684 caused dose-dependent sedation. No serious adverse events occurred. The volume of distribution and clearance of Ro 48-8684 were larger than of midazolam (337+/-114 vs 50+/-121 and 2.4+/-0.5 vs 0.47+/-0.11 l min(-1), resp). The recovery of saccadic eye movements from equal levels of sedation was on average almost half an hour faster for Ro 48-8684 than for midazolam, with considerable interindividual differences (range 2, 55 min). The doses of Ro 48-8684 leading to the same clinical endpoint as midazolam were comparable, but the corresponding predicted effect compartment concentrations of Ro 48-8684 were on average 2.6 times lower (range 1.5, 4.9 times). The slope of the linear concentration-effect-relationship for saccadic peak velocity was on average 2.2 times steeper for 10 mg Ro 48-8684 than for midazolam (range 1.3, 3.3). The slope decreased on average 4.4-fold (range 1.6, 7.3 times), with doses of Ro 48-8684 increasing from 1 to 10 mg. The metabolite Ro 61-2466 had a longer half-life than the parent compound Ro 48-8684. The influence of this metabolite during prolonged administration should be further investigated. CONCLUSIONS: These results show that Ro 48-8684 has a considerably shorter duration of action than midazolam. There may be a reduction of sensitivity to Ro 48-8684 with repeated administration of rising doses due to as yet undetermined factors.

Adult↗
PubMed1998

Midazolam pharmacokinetics following intravenous and buccal administration.

AIMS: Midazolam has good anxiolytic qualities and is a well established premedication agent before anaesthesia or short surgical procedures. The objective of the present study was to determine pharmacokinetic data from individual plasma concentration profiles obtained following intravenous and buccal administration of midazolam. METHODS: Eight young healthy volunteers received single doses of 5 mg midazolam i.v. and after a period of 1 week buccally in a cross over manner. Blood samples were obtained up to 480 min. The measurement of plasma midazolam concentrations was by gas-chromatography. RESULTS: The maximum plasma concentration was 55.9 ng ml(-1) (range 35.6-77.9 ng ml(-1)) at 30 min (range 15-90 min) following buccal administration. AUC was calculated to be 15016 ng ml(-1) min (s.d. 3778 ng ml(-1) min) following i.v. and 11191 ng ml(-1) min (s.d. 1777 ng ml(-1) min) following buccal midazolam. This gave a mean midazolam bioavailability of 74.5%. CONCLUSIONS: The pharmacokinetic data presented in this study demonstrate a high bioavailability and reliable plasma concentrations following buccal midazolam. The clinical benefit of buccal midazolam may be in particular patient controlled premedication or sedation in adults.

Administration, Buccal↗
PubMed2002

Absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers.

AIMS: Midazolam is given intravenously for induction of anaesthesia and conscious sedation and by subcutaneous infusion in patients in palliative care units. The objective of the present study was to determine the absolute bioavailability of subcutaneous midazolam and its pharmacokinetics in young, healthy, male volunteers. METHODS: Eighteen volunteers were given single doses of 0.1 mg kg-1 midazolam i.v. and s.c. after a wash-out period of 7-15 days in an open-label, randomized, cross-over study. Blood samples were collected up to 12 h post-infusion. Plasma concentrations of midazolam and of its two metabolites, 1'-OHM and 4-OHM, were assessed using an h.p.l.c.-MS method (LOQ 0.5 ng ml-1 for each analyte). Vital signs, cardiac parameters and oximetry were monitored. Local tolerance was determined and adverse events were also monitored. RESULTS: After s.c. infusion t(max) and C(max) were 0.51 +/- 0.18 h and 127.8 +/- 29.3 ng ml-1 (mean +/- s.d.), respectively. No statistically significant difference was detected in AUC(0, infinity ) after i.v. and s.c. administration. The mean (+/- s.d.) absolute bioavailability of subcutaneous midazolam was 0.96 (+/- 0.14) (CI 0.84, 1.03). Mean (+/- s.d.) t1/2 was similar after s.c. (3.2 (+/- 1.0) h) and i.v. infusion (2.9 (+/- 0.7) h), although a statistically significant difference was reached (P < 0.05). Mean CL and V of i.v. midazolam were 4.4 +/- 1.0 ml min-1 kg-1 and 1.1 +/- 0.2 l kg-1 (mean +/- s.d.), respectively. Plasma concentrations of 1'-OHM were higher than those of 4-OHM. Few mild and transient adverse events were noted and there were no clinically significant effects on EEG, blood pressure and laboratory parameters. CONCLUSIONS: This study has shown that subcutaneous midazolam has excellent bioavailability and that administration of midazolam by this route could be preferable when the intravenous route is inappropriate.

Adult↗
PubMed2004

Comparative population pharmacokinetics of lorazepam and midazolam during long-term continuous infusion in critically ill patients.

AIMS: It is well established that there is a wide intra- and interindividual variability in dose requirements for lorazepam and midazolam in intensive care patients. The objective of this study was to compare the population pharmacokinetics of lorazepam and midazolam after long-term continuous infusion in mechanically ventilated critically ill patients. METHODS: Forty-nine critically ill patients randomly received either lorazepam (n = 28) or midazolam (n = 21) by continuous infusion for at least 24 h. Multiple blood samples were obtained for determination of the drug and metabolite concentrations by HPLC. Population pharmacokinetic models were developed using the Non-Linear Mixed Effect Modelling (NONMEM) program. The influence of selected covariates was investigated. The prospective performance of the models was evaluated on the basis of results in separate groups of patients for lorazepam (n = 31) and midazolam (n = 33). RESULTS: The pharmacokinetics of lorazepam were best described by a two-compartment model. Alcohol abuse, positive end expiratory pressure (PEEP) and age were identified as significant covariates. Total body clearance for patients without alcohol abuse was 4.13 - (PEEP - 5) x 0.42 l h-1, and 0.74 l h-1 for patients with alcohol abuse. The volume of distribution was 0.74 l, the steady state volume of distribution was 56 - (age - 58) x 2.1 l and the intercompartmental clearance was 10 l h-1. The proportional residual error was 15% and the median absolute prediction error was 13.6% with a bias of 1.5%. The pharmacokinetics of midazolam were best described by a two-compartment model with alcohol abuse, APACHE score and age as significant covariates. Total body clearance for patients without alcohol abuse was 11.3 - (age - 57) x 0.14 l h-1, and 7.27 - (age -57) x 0.14 l h-1 for patients with alcohol abuse. The volume of distribution was 7.15 l, the steady state volume of distribution was 431 l, and the intercompartmental clearance was 40.8 - (APACHE score - 26) x 2.75 l h-1. The proportional residual error was 31% with an additive residual error of 32 ng ml-1. The median absolute prediction error was 12.9% with a bias of 1.2%. The prospective performance in the lorazepam evaluation group was better with the covariate adjusted model, but in the midazolam evaluation group it was not better than with the simple model. In all models a tendency to overestimate the lower plasma concentrations was observed. CONCLUSIONS: The pharmacokinetics of both lorazepam and midazolam were well described by a two-compartment model. Inclusion of alcohol abuse and age as covariates improved both models. PEEP was identified as an additional covariate for lorazepam, and the APACHE score for midazolam. For both drugs there is a large interindividual variability in their pharmacokinetics when used for long-term sedation in critically ill patients. However, the intra-individual variability is much lower for lorazepam.

Adolescent↗
PubMed2002

Controlling seizures in the prehospital setting: diazepam or midazolam?

OBJECTIVE: To determine which is the most effective and safe treatment for controlling seizures in children out-of-hospital: diazepam or midazolam. METHODS: A retrospective review of the medical records of children presenting to the Emergency Department of the Children's Hospital at Westmead (CHW-ED) with seizures requiring treatment in the field by paramedics was carried out over a 4-year period (April 1996 to March 2000). In New South Wales, children with seizures in the prehospital setting received 0.5 mg/kg per rectum (p.r.) or 0.1 mg/kg i.v. diazepam until March 1998 and from March 1997 onwards they received 0.15 mg/kg i.m. or 0.1 mg/kg i.v. midazolam. The main outcome measured was cessation of seizure in the prehospital setting. Secondary outcomes were time taken to initiate treatment and the frequency of cardiorespiratory compromise. RESULTS: Over the 4-year period, 2566 children presented to CHW-ED with a seizure; 107 children were eligible for entry into the present study. Of these 107 patients, 62 received diazepam and 45 received midazolam. Thirty-one (50.0%) in the diazepam group and 15 (33.3%) in the midazolam group were febrile seizures. Both groups were similar in terms of demographics and seizure type. A comparison of diazepam with midazolam showed that both drugs were effective in stopping seizures within 5 min of drug administration (37.1% cf. 51.1%). Fewer patients in the midazolam group suffered apnoea (20.0% cf. 29.0%; P < 0.05). CONCLUSION: Midazolam controls seizures as effectively as diazepam in the prehospital setting. Furthermore, midazolam potentially reduces respiratory depression and time to treatment.

Anticonvulsants↗
PubMed2003

A paediatric trial comparing midazolam/Syrpalta mixture with premixed midazolam syrup (Roche).

BACKGROUND: The bitter taste of midazolam is more acceptable to children when the drug is mixed with fruit juice or syrup. We use a thick grape syrup (Syrpalta), and children are sedated in 10-15 min. A premixed cherry-flavoured midazolam solution (Roche), 2 mg.ml (-1), is currently available. It has been our impression that the premixed midazolam has a slower onset of action. Our aim was to evaluate the effects of the midazolam mixtures (midazolam 0.5 mg.kg (-1), 2 mg.ml (-1)) on children's anxiety, sedation, separation anxiety, mask acceptance, and recovery time. METHODS: Seventy-six healthy children, 1-4 years of age, scheduled for elective placement of ear tubes, were enrolled. The trial was double-blinded and randomized. For premedication, one group received the premixed midazolam, and a second group received the midazolam/Syrpalta mixture. An independent blinded observer evaluated the children, using anxiety and sedation scales at baseline, at 5, 10 and 15 min and at parental separation. Mask acceptance and awakening time were evaluated. RESULTS: Children who received the midazolam/Syrpalta mixture had less anxiety at 15 min (P = 0.046) and at parental separation (P < 0.001) than those who received the premixed midazolam solution. Mask acceptance was not different. CONCLUSIONS: We concluded that the midazolam/Syrpalta mixture has a faster onset of action than the premixed midazolam solution.

Administration, Oral↗
PubMed2002

[Co-maintenance with propofol and midazolam: sympathoadrenergic reactions, hemodynamic effects, stress response, EEG and recovery].

OBJECTIVE: The study was undertaken to investigate the influence of TIVA with propofol, midazolam and fentanyl (comaintenance, COM-group) or TIVA with propofol and fentanyl (control-group) on sympathoadrenergic and hemodynamic reactions, stress response, EEG and recovery. METHODS: After ethical approval, 2 x 20 patients of ASA-risk I - III over 55 years of age undergoing visceral surgery were investigated in a prospective randomized design. For induction of anesthesia, patients of the COM-group received 0,05 mg/kg BW midazolam und 1,0 mg/kg BW propofol, and anesthesia was maintained with 0,05 mg/kg BW/h midazolam (until 15 - 30 min before the end of the operation) together with propofol in decreasing doses of 10 - 5 - 2 mg/kg BW/h. In the control-group, 2,0 mg/kg BW propofol were used for induction followed by decreasing doses of 10 - 5 - 2 mg/kg BW/h as well. Premedication (0,1 mg/kg BW midazolam orally) and weight-dependent doses of fentanyl (2,5 microgram/kg BW for induction, 1,25 microgram/kg BW 2 min before skin incision, further repetition doses of 1,25 - 2,5 microgram/kg/BW as required) and vecuronium were equal in both groups. Beyond consumption of anesthetics and recovery, sympathoadrenergic, other endocrine and hemodynamic reactions and SEF 90 were investigated at 7 time points before induction and postoperative recovery. alpha </= 0,05 was considered significant. RESULTS: Biometric data (mean age > 70 years) and duration of anesthesia and operation were comparable in both groups. Consumption of midazolam was higher in the COM-Group (14,8 vs. 7,5 mg; p = 0,004), whereas doses of fentanyl and vecuronium were comparable in both collectives. Recovery was significantly (p = 0,004) delayed in the COM-group: observing of simple orders 12,6 vs. 5,8 min, orientation with respect to person 19,8 vs. 9,9 min, local orientation 23,1 vs. 11,3 min. Mean arterial pressure in the COM-group was throughout lower than in the control-group, whereas heart rate was higher during the course of operation. Endocrine stress parameters (adrenaline, noradrenaline, antidiuretic hormone, adrenocorticotropic hormone, cortisol) and spectral edge frequency (SEF 90; Dräger-pEEG) were comparable in group level and time course between both groups. Plasma-concentrations of midazolam were significantly higher in the COM-group. CONCLUSION: In elderly patients undergoing visceral surgery in TIVA and when compared with propofol alone, no benefit of coinduction and comaintenance with midazolam and propofol could be demonstrated with respect to hemodynamic reactions and sympathoadrenergic and other endocrine stress response as well. Recovery was significantly delayed after administration of midazolam.

Aged↗
PubMed1997

[The dose-dependent effects of oral premedication with midazolam].

OBJECTIVE: The aim of this study was to examine the psychological effects, well-being and side effects after various doses of oral midazolam medication. METHODS: After informed consent has been obtained and following the approval by the institutional ethical committee, 80 adult patients in the ASA physical status I and II were randomly assigned to one of five different premedication groups: 3.75, 7.5, 11.25, 15 mg midazolam, and placebo. The medication was given in a double-blind fashion 60 min before induction of general anaesthesia for various surgical procedures. At 3 definite stages (before premedication, 30 and 60 min after premedication), blood pressure, heart rate, transcutaneous oxygen saturation and respiratory rate were measured. Sedation and well-being were graded according to a 5-point scale, and the subjective anxiety level was assessed according a visual analogue scale (range 0-100 mm). Anterograde and retrograde amnesia were measured by recall of auditive and visual stimuli. Finally, patients were asked whether in case of future surgery they would prefer the same or a different medication. RESULTS: Demographic data were similar in all groups. There was no significant difference in respiratory rate, oxygen saturation, blood pressure or heart rate. Alertness declined only after 60 min in the groups treated with 7.5 mg and more midazolam. During the entire measurement period, anxiolysis was not different from placebo in any of the midazolam groups. In comparison to placebo, all midazolam groups showed a statistically significant and dose dependent anterograde amnesia for visual stimuli. Subjective well-being scores showed no differences between the groups. Only few side effects were seen following doses of 7.5 mg and higher, including ptosis, strabismus, diplopia, speech disorders, disorientation and vertigo. The majority of patients in all groups indicated a wish for the same medication in case of future anaesthesia for surgical interventions. CONCLUSIONS: Midazolam administered orally prior to surgical procedures showed marked interindividual variability. Sedation and amnesia were dose-dependent and were evaluated by the patients as acceptable. Anxiolysis was not significantly different from placebo. A dose of 7.5 mg midazolam showed the best relation between desirable and undesirable effects. Adequate attention given to the patient by the anaesthesiologist prior to surgery seems to be as important and beneficial as oral medication with midazolam.

Administration, Oral↗
PubMed2002

Application of semisimultaneous midazolam administration for hepatic and intestinal cytochrome P450 3A phenotyping.

OBJECTIVES: Determination of hepatic and intestinal cytochrome P450 (CYP) 3A activity is important, because CYP3A substrates show substantial variability in plasma concentrations as a result of variations in both hepatic and intestinal metabolism. The goals of this study were (1) to determine whether the hepatic and intestinal extraction ratios (ER(H) and ER(G), respectively) of the CYP3A probe drug midazolam are different when determined after semisimultaneous administration, as compared with administration on separate occasions (traditional method), and (2) to evaluate the hepatic and intestinal metabolism of midazolam in the presence and absence of ketoconazole by the semisimultaneous method. METHODS: Midazolam pharmacokinetics was assessed in 12 healthy volunteers after administration of midazolam, 5 mg orally, followed at 6 hours by 2 mg given by intravenous infusion. Concentration-time data were fitted to a combined oral-intravenous infusion model by nonlinear regression (semisimultaneous method). Data from the semisimultaneous method were compared with those obtained after individual midazolam doses, 1 week apart (traditional approach). The effect of ketoconazole on midazolam pharmacokinetics after semisimultaneous administration was also determined in 4 healthy volunteers. RESULTS: There were no significant differences in bioavailability (0.343 +/- 0.100 versus 0.343 +/- 0.094), ER(H) (0.269 +/- 0.064 versus 0.267 +/- 0.077), and ER(G) (0.534 +/- 0.135 versus 0.531 +/- 0.124) between the traditional and semisimultaneous methods. As expected, ketoconazole markedly increased the mean bioavailability to 0.838 (2.4-fold), the mean ER(H) was decreased 3.7-fold, and the mean ER(G) was decreased 5.7-fold. CONCLUSIONS: Midazolam pharmacokinetic parameters that are specific to liver and intestinal metabolism were not different between the traditional and semisimultaneous methods. The semisimultaneous method also yielded expected marked changes in the parameters as a result of ketoconazole inhibition. Thus the semisimultaneous midazolam method appears to be a suitable approach to determine hepatic and intestinal CYP3A activity at baseline and with enzyme inhibition.

Administration, Oral↗
PubMed2002

A controlled study of the effect of midazolam on abnormal sphincter of Oddi motility.

BACKGROUND: The effect of a medication on sphincter of Oddi motility should be characterized if it is to be used during sphincter of Oddi manometry. Controversy exists as to whether midazolam influences sphincter of Oddi motility. This study assessed the effect of midazolam on the hypertensive sphincter of Oddi. METHODS: The study population consisted of 36 patients who presented with recurrent abdominal pain resulting from sphincter of Oddi dysfunction. The study was nonrandomized, prospective, and placebo controlled. Patient allocation was consecutive. Sphincter of Oddi manometry was performed in standard fashion. Manometric tracings were interpreted while the investigator was blinded to treatment allocation. Eighteen patients in the test group received 2 mg of midazolam intravenously whereas the 18 patients in the control group received saline solution intravenously. Manometric parameters were measured before and 3 minutes after the intravenous infusion. Changes in manometric findings before and after the administration of saline solution and midazolam were compared. RESULTS: Midazolam caused a significant reduction in basal sphincter of Oddi pressure (24 mm Hg) as compared with saline solution (p < 0.001). Diagnostic concordance (normal vs. abnormal) between the basal sphincter pressure before and after midazolam was seen in only 77% of patients. CONCLUSIONS: Midazolam significantly altered sphincter of Oddi motility. The decrease in sphincteric pressures would have altered diagnosis and management in 4 of 18 patients. Midazolam should not be used during sphincter of Oddi manometry.

Adult↗
PubMedDate not supplied

The use of midazolam for prehospital rapid-sequence intubation may be associated with a dose-related increase in hypotension.

OBJECTIVE: To investigate the incidence of hypotension associated with the use of midazolam for prehospital rapid-sequence intubation (RSI). METHODS: A retrospective review was performed using charts from the two aeromedical agencies servicing the authors' region. The RSI protocols used by crews from the northern (north) and the southern (south) parts of the region were identical, with the exception of midazolam dosing. The north crews used 0.1 mg/kg for all patients, while the south crews used 0.1 mg/kg up to a maximum of 5 mg. All patients receiving midazolam for prehospital RSI were pooled, with multiple linear regression used to investigate the relationship between midazolam dose and both hypotension and a decrease in systolic blood pressure (SBP) following RSI. Patients weighing >50 kg and patients with traumatic brain injury (TBI) were evaluated separately to determine differences between north and south with regard to midazolam dosing and incidence of hypotension. Multivariate logistical regression was used to test for these differences and for potential confounders such as age, initial SBP, and Glasgow Coma Scale score (GCS). RESULTS: A total of 219 patients were identified from the north (n = 75) and the south (n = 144). Multiple linear regression revealed a statistically significant relationship between midazolam dose and both hypotension and an SBP decrease following RSI. There was no difference between north and south with regard to age, sex, incidence of TBI, initial SBP, or GCS. In patients >50 kg, those from the north received higher doses of midazolam and had a higher incidence of hypotension than those from the south. This relationship was also present in 184 patients with TBI. CONCLUSION: The use of midazolam with prehospital RSI is associated with a dose-related incidence of hypotension.

Adult↗
PubMedDate not supplied

The effectiveness of midazolam as a single pharmacologic agent to facilitate endotracheal intubation by paramedics.

OBJECTIVE: Endotracheal intubation (ETI) remains the "gold standard" for securing a patient's airway. In recent years, the use of pharmacologic agents to assist paramedics achieve successful intubation of problematic airways has become more common. This study was done to determine the efficacy of intravenous midazolam, a short-acting benzodiazepine, as a drug to facilitate intubation in patients resistant to conventional ETI. METHODS: This retrospective observational study reviewed the 22-month experience of a suburban municipal EMS system after midazolam was introduced as an agent to be used for systemic sedation to facilitate ETI. All calls where midazolam was used were reviewed on a monthly basis by investigators via retrospective review of the prehospital care reports. RESULTS: During the study period 13,212 emergency responses occurred, resulting in 154 ETIs by paramedics. Midazolam was used to facilitate 20 (13%) of these ETIs. "Clenched teeth" and failed conventional intubation were the most commonly cited indications for facilitated intubation. Eleven patients had medical complaints and nine were trauma patients. Successful ETI with midazolam was achieved in 17 of 20 (85%) cases. In 85% (15 of 17) of these cases, a single dose of midazolam was sufficient for ETI [mean dose 3.6 mg (SD 1.1 mg)]. The three patients with failed ETI received multiple doses of midazolam [mean dose 5.0 mg (SD 2.0 mg)]. CONCLUSION: The prehospital use of single-dose IV midazolam is generally effective in accomplishing facilitated ETI in patients resistant to conventional (nonpharmacologic) ETI.

Allied Health Personnel↗
PubMed1982

Effect of different kinds of premedication on the induction properties of midazolam.

The effects of different premedication (i.m. and i.v.) on the usefulness of midazolam or thiopentone as induction agents for minor surgery was studied in 194 women undergoing either dilatation and curettage or explorative fractionate curettage. Midazolam appeared to produce light sedation which required powerful premedication (i.m. atropine + pethidine and i.v. fentanyl or fentanyl + dehydrobenzperidol) when used as an induction agent for minor surgery. The clinically useful dose of midazolam is about 0.30 mg kg-1 i.v. There was greater variability in onset and duration of action among patients receiving midazolam than among those receiving thiopentone. Midazolam caused less respiratory depression, but there were no clinically significant differences between midazolam and thiopentone with respect to cardiovascular variables. Muscular movements were found more often, and postoperative sedation lasted longer in patients receiving midazolam. Midazolam as an induction agent appears more suited for major than for minor surgery.

Adult↗
PubMed2002

Auditory evoked response during propofol anaesthesia after pre-induction with midazolam.

BACKGROUND: In clinical use, midazolam reduces the dose requirement for propofol. We studied the effect of midazolam given before anaesthesia on the amount of propofol needed and the time taken, to achieve loss of consciousness (LOC) in 20 patients. METHODS: We compared the auditory evoked responses (AER) in these patients with those in a group of 20 patients who were not given midazolam. RESULTS: LOC, as defined by a loss of response to verbal command and eyelash reflex, occurred after 113 (95% CI, 99-131) s in the control group and 75 (56-101) s in the midazolam group (P < 0.05). In the control group 2.3 (2.0-2.6) mg kg-1 propofol caused LOC compared with 1.3 (1.1-1.5) mg kg-1 in the group pretreated with midazolam (P < 0.001). Pa amplitude decreased by 60% in the control group and by 54% in the midazolam group while Nb latency increased by 24% in the control group and by 32% in the midazolam group following LOC. These differences were not significant. CONCLUSIONS: We confirmed that coinduction of anaesthesia with midazolam and propofol reduces the requirement of propofol. We also demonstrated that the AER reflects anaesthetic depth rather than plasma concentrations of anaesthetic drugs.

Adult↗
PubMed1997

Effects of midazolam on contractions in smooth muscle of the rabbit mesenteric artery.

We investigated the undetermined effects of midazolam on agonist-induced contraction in vascular smooth muscle strips from the rabbit mesenteric resistance artery. Midazolam, in concentrations more than 10 microM, attenuated norepinephrine ([NE] 0.3-10 microM)-induced contractions in Krebs solution. The attenuating effect was more potent on the tonic and oscillatory responses than on the rapid phasic response. When voltage-operated Ca2+ channels (VOC) were blocked by nifedipine, midazolam, in concentrations more than 1 microM, attenuated both phasic and tonic responses. In Ca(2+)-free solution, midazolam, in concentrations more than 1 microM, attenuated NE-induced contractions, but not caffeine-induced contractions. When NE and caffeine were applied successively, midazolam attenuated NE-induced contractions, but enhanced caffeine-induced contractions. Because the attenuating effect of midazolam on NE-induced contractions in high K+, Ca(2+)-free solution were not different from the effect in normal Ca(2+)-free solution, the attenuating effects of midazolam could not have been induced via membrane hyperpolarization. These results indicate that midazolam attenuated the agonist-induced contractions by inhibition of Ca2+ influx occurring not only through VOC, but also through agonist-mediated Ca2+ channels and by the inhibition of Ca2+ release from intracellular store sites.

Adrenergic alpha-Agonists↗