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PubMed2006

Dexmedetomidine and meperidine prevent postanaesthetic shivering.

BACKGROUND AND OBJECTIVE: This placebo-controlled study was performed to evaluate the efficacy of dexmedetomidine compared with meperidine and placebo in preventing postanaesthetic shivering. METHODS: We studied 120 patients (ASA I-II) scheduled for elective abdominal or orthopaedic surgery of about 1-3 h duration. Forty patients in each group randomly received 1 microg kg(-1) of dexmedetomidine, 0.5 mg kg(-1) of meperidine or saline 0.9% as placebo, intravenously (i.v.). Mean arterial pressure, heart rate, oxygen saturation and central body temperature were measured. Extubation, awakening and orientation times, shivering, pain, recovery and sedation scores were recorded. RESULTS: Postanaesthetic shivering was seen in 22 patients in the placebo group, four patients in the meperidine group and six patients in the dexmedetomidine group. Sedation scores were significantly higher in the dexmedetomidine group compared with meperidine and placebo groups. Both dexmedetomidine and meperidine caused a significantly prolonged extubation and awakening time compared with placebo. Also, dexmedetomidine caused a significantly prolonged orientation time compared with other two groups. CONCLUSION: Intraoperative intravenously administration of dexmedetomidine 1 microg kg(-1) reduces postanaesthetic shivering as does meperidine 0.5 mg kg(-1) in patients after major surgery.

Adolescent↗
PubMed1980

Meperidine disposition in mother, neonate, and nonpregnant females.

Whether meperidine metabolism is affected by pregnancy or immaturity has not been clearly established. This is of interest because meperidine is commonly given during labor for pain relief and the fetus receives the drug in utero. Moreover, animals studies suggest that the hormones of pregnancy contribute to decreased activity of the drug-metabolizing enzymes. In our study gas chromatography was used to determine the concentrations of meperidine and normeperidine in the plasma and urine of pregnant and nonpregnant women and in the urine of neonates. Plasma samples were collected for at least 3 hr after a dose of meperidine intravenously to calculate the kinetic parameters of meperidine disposition; urine samples were collected for 3 days. In contrasts to reports on animals, we found that pregnant and nonpregnant women readily metabolize meperidine to normeperidine and excrete both in a similar manner. No significant differences were demonstrated between any of the kinetic constants for peripartum and nonpregnant subjects. The neonate was found to metabolize and excrete these drugs less rapidly.

Adolescent↗
PubMed1981

Meperidine disposition in man: influence of urinary pH and route of administration.

The effects of route of administration and altered urinary pH on the disposition of meperidine and its metabolite normeperidine were investigated in six normal, nonsmoking young men from 23 to 31 yr old. Meperidine (21.75 mg) was injected intravenously simultaneous with the same dose of deuterated (2H5) drug given orally in solution or by injection into the deltoid muscle. After intravenous administration with no control of urinary pH, meperidine blood levels declined triexponentially over 24 hr with a terminal half-life (t1/2) of 4.9 to 9.4 hr and a clearance of 472 to 686 ml/min. The 48-hr urinary recoveries of meperidine and normeperidine were about 7% and 12%. Urinary acidification with ammonium chloride reduced these amounts to less than 1% and about 7%, whereas urinary alkalinization increased them to about 20% and 24%. These pronounced changes had negligible effects on the blood concentration/time profiles. Plasma levels were proportional to the blood concentrations with a ratio of about unity for meperidine and a value 25% greater for normeperidine. Absorption after intramuscular injection was complete and followed a first-order process with t1/2 ranging from 7 to 13 min. Accordingly, maximum blood levels were achieved within 5 to 15 min and the concentration was essentially the same as after intravenous dosing. In contrast, oral bioavailability was incomplete, ranging from 47% to 73%, and at a much slower rate, with peak concentrations being observed after about 1 hr. Absorption was biphasic and was preceded by a 5- to 10-min lag period. Normeperidine blood concentration after intravenous dosing reached a maximum within 2 to 4 hr and remained at this value through 12 hr before modestly declining by 24 hr. After oral dosing the peak level was achieved more rapidly and sharply. Thus, presystemic elimination occurs after oral dosing within meperidine consistent in value with the measured blood clearance which, therefore, probably reflects only hepatic metabolism.

Administration, Oral↗
PubMed1983

Metkephamid and meperidine analgesia after episiotomy.

Metkephamid is an analog of methionine enkephalin. The efficacy, safety, and time course of analgesia with 70 or 140 mg metkephamid were compared with those of 100 mg meperidine and placebo in 59 hospitalized women with severe postpartum episiotomy pain. There were two separate trials with single intramuscular doses and identical designs, including parallel groups, randomized blocks, and double-blind conditions. Using subjective reports as indexes of response, patients rated pain intensity, pain relief, and side effects at periodic interviews for 6 hr. Almost all measures of summed and peak analgesia exhibited important differences among the three treatments in both trials. Metkephamid at the 140-mg dose was the most effective and meperidine, 100 mg, was next, whereas metkephamid, 70 mg, and placebo were least effective. Only metkephamid, 140 mg, and meperidine were measurably superior to placebo. Both treatments took effect within 30 min and peaked at 1 to 2 hr; with 140 mg metkephamid, maximum analgesia was sustained 6 hr, i.e., 2 hr longer than with meperidine. Metkephamid, 70 mg, could not be distinguished from placebo throughout its entire time course. Although dizziness was experienced with meperidine, the two metkephamid doses induced other side effects, including sensation of heavy limbs, dry mouth, eye redness, and nasal stuffiness. None were distressing. Our results suggest that 140 mg metkephamid compares favorably with 100 mg meperidine for analgesia after episiotomy, but it induces minor side effects more frequently.

Adolescent↗
PubMed1988

Pharmacokinetic profile of epidural meperidine with and without dextran 70.

To evaluate the effect of dextran 70 on the kinetics of epidural meperidine, 10 female patients anesthetized with nitrous oxide and halothane were studied. Meperidine, 1 mg.kg-1, was administered epidurally in either 10 ml dextran 70 in saline solution (group I) or 10 ml saline solution (group II, control subjects). Plasma concentration of meperidine was determined for 10 hours after its administration with GC. Meperidine plasma concentration-time curves could be best resolved into three exponential terms with a lag time in both groups of patients. The disposition kinetics were described adequately by a three-compartment model. This study demonstrated that apart from a significantly longer lag time and smaller k10 (apparent first-order rate constant for elimination of meperidine from the central compartment), the addition of dextran did not alter significantly the kinetic parameters of epidural meperidine.

Adult↗
PubMed2002

Addition of meperidine to bupivacaine for spinal anaesthesia for Caesarean section.

BACKGROUND: In a prospective, randomized, double-blind, placebo-controlled trial, we investigated the effect of adding meperidine 10 mg to intrathecal bupivacaine on the duration of early postoperative analgesia in 40 patients having elective Caesarean section under spinal anaesthesia. METHODS: Patients received intrathecal injection of 0.5% hyperbaric bupivacaine 2.0 ml plus either normal saline 0.2 ml (saline group) or 5% meperidine 0.2 ml (meperidine group). After operation, all patients were given i.v. patient-controlled analgesia using morphine. RESULTS: The duration of effective analgesia, defined as the time from intrathecal injection to first patient-controlled analgesia demand, was greater in the meperidine group (mean 234 min, 95% confidence interval 200-269 min) compared with the saline group (mean 125 min, 95% confidence interval 111-138 min; P<0.001). The 24 h morphine requirement was similar in the two groups. The meperidine group had a greater incidence of intraoperative nausea or vomiting compared with the saline group (11 vs 3; P=0.02). CONCLUSION: Addition of meperidine 10 mg to intrathecal bupivacaine for Caesarean section is associated with prolonged postoperative analgesia but with greater intraoperative nausea and vomiting.

Adjuvants, Anesthesia↗
PubMed1995

Intravenous regional anesthesia with meperidine.

Forty-five ASA physical status I volunteers, divided in three groups of 15 each, received intravenous regional anesthesia (IVRA) of the upper limb with 40 mL meperidine 0.25%, lidocaine 0.5%, or 0.9% sodium chloride (isolated ischemia) by random allocation. Using a double-blind method, the onset and recovery of sensory block was tested at six sites of the forearm and hand. The onset of complete motor block was also assessed. The symptoms after deflation of the tourniquet were recorded. The onset of block, as determined by pin-prick touch, and cold was significantly faster in the meperidine group (P < 0.001) than in the saline group, but also slower (P < 0.001) than in the lidocaine group. After the tourniquet was deflated, recovery occurred in reverse order. A complete motor block was noted in all volunteers from the meperidine and lidocaine groups, but in only 11 cases from the 0.9% sodium chloride group (P < 0.01). In the meperidine group, motor block developed concomitantly or prior to sensory block. There was a significant increase in the incidence of dizziness, nausea, and pain at the injection site in the meperidine group in comparison with the lidocaine group. We conclude that meperidine has local anesthetic action on the peripheral nerve in vivo, but that its single use for IVRA should be a second choice for patients allergic to local anesthetics.

Adolescent↗
PubMed1998

The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study.

UNLABELLED: Using venous retention with a tourniquet (70 mm Hg), we performed a randomized, double-blind study to assess the efficacy of I.V. pretreatment with fentanyl, morphine, meperidine, or lidocaine in reducing propofol injection pain. Immediately after venous occlusion with a tourniquet, I.V. fentanyl 150 microg (Group A, n = 35), morphine 4 mg (Group B, n = 35), meperidine 40 mg (Group C, n = 35), 2% lidocaine 3 mL (Group D, n = 35), or normal saline 3 mL (Group E, n = 35; as placebo control) was given to adult patients. The venous retention of the drug was maintained for 1 min, followed by tourniquet release and I.V. administration of propofol 100 mg. Pain assessment was made immediately after the propofol injection. Lidocaine and meperidine significantly reduced propofol injection pain more than placebo (P < 0.05), but there were more side effects in the meperidine group. Fentanyl and morphine reduced the intensity of propofol injection pain (P < 0.05) and had some effect in reducing the incidence of propofol injection pain, but the difference did not reach statistical significance. The order of efficacy was lidocaine approximately meperidine > morphine approximately fentanyl. We postulate that the peripheral analgesic effect of these opioid is due to their local anesthetic activity. IMPLICATIONS: Propofol, a commonly used anesthetic, often causes pain on injection. Given as venous retention pretreatments 1 min before propofol, meperidine and lidocaine were found to significantly reduce the propofol injection pain, whereas fentanyl and morphine only slightly reduced the propofol injection pain.

Adult↗
PubMed2000

An assessment of the value of intraperitoneal meperidine for analgesia postlaparoscopic tubal ligation.

UNLABELLED: Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P: < 0.01) and with movement (P: < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation. IMPLICATIONS: The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.

Adult↗
PubMed2001

Remifentanil versus meperidine for monitored anesthesia care: a comparison study in older patients undergoing ambulatory colonoscopy.

UNLABELLED: Colonoscopy is one of the most frequently performed outpatient procedures in the United States. This study was designed to test the hypothesis that a remifentanil infusion would be superior to boluses of meperidine in older patients undergoing ambulatory colonoscopy. One hundred ASA physical status I-IV patients undergoing colonoscopy were randomized in this double-blinded study to receive either remifentanil infusions (n = 49) or titrated boluses of meperidine (n = 51). Patient tolerance was assessed using physiologic variables and side effects associated with opioid analgesia. Verbal pain/anxiety and patient/operator satisfaction were also assessed. As a group, the physiologic characteristics demonstrated no significant differences in the response to the colonoscopy procedure. Although the patient and operator satisfaction surveys were similar between groups, the incidences of tachycardia, hypotension, and nausea were less and the adjusted verbal pain and anxiety scores were more in the Remifentanil group compared with the Meperidine group. This study demonstrates that remifentanil and meperidine were equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. The differences in the pharmakinetics of remifentanil and meperidine most likely account for the differences noted between the two treatment groups. IMPLICATIONS: Remifentanil infusions and meperidine boluses are equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider.

Adjuvants, Anesthesia↗
PubMed2001

A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering.

UNLABELLED: Postanesthetic shivering can be treated with many types of drugs. We compared the effects of meperidine, clonidine, and urapidil on postanesthetic shivering. Sixty patients shivering during recovery from general anesthesia were treated in a randomized, double-blinded fashion with 25 mg meperidine IV, 0.15 mg clonidine IV, or 25 mg urapidil IV in three separate groups of 20 patients each. If shivering did not stop within 5 min, the treatment was repeated once; clonidine was replaced with saline for the second dose. Rectal temperature, arterial blood pressure, heart rate, SaO(2) and vigilance were monitored. Clonidine stopped shivering in all 20 patients. A single dose of meperidine stopped the shivering in 18 of 20 patients, with the other 2 patients needing a second dose. Urapidil was less effective: the first dose stopped the shivering in only six patients; the second dose was effective in another six; the drug was ineffective in 8 of 20 patients. Meperidine and clonidine were both nearly 100% effective in treating postanesthetic shivering without negative side effects. By comparison, urapidil was only effective in 60% of patients treated (P <0.01). IMPLICATIONS: Patients shivering during recovery from general anesthesia were treated in a randomized double-blinded fashion with meperidine, clonidine, or urapidil. Meperidine and clonidine were both very effective, whereas urapidil was only effective in 60% of patients treated.

Adrenergic alpha-Agonists↗
PubMed1994

Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration.

BACKGROUND: Although meperidine has been used for patient-controlled analgesia both intravenously (PCIA) and epidurally (PCEA), these routes have not been compared, and many studies have suggested that there is no advantage to the epidural route for administration of lipophilic opioids. METHODS: A randomized, double-blind, crossover study was conducted for 24 h after cesarean section to compare the analgesic efficacy, side effects, patient satisfaction, drug use, and plasma drug concentrations with meperidine administered either as PCIA or as PCEA. Two groups, stratified for time of cesarean section during epidural anesthesia, postoperatively received either PCEA (group 1) or PCIA (group 2) with identical variables for 12 h before crossing to the other route for an additional 12 h. RESULTS: Results from 45 patients showed a similar speed of analgesic onset but, subsequently, significantly lower pain scores both at rest and with coughing in those receiving PCEA (P = 0.0001). Nausea and pruritus scores did not differ between the groups in the first 12 h postoperatively, but sedation scores were significantly higher with PCIA (P = 0.0001). Patient satisfaction scores and preference significantly favored PCEA (P = 0.0001), with almost 90% of participants preferring the epidural route. Meperidine use was reduced approximately 50% with PCEA (P = 0.0001), and plasma meperidine and normeperidine concentrations were significantly lower (P = 0.0001). CONCLUSIONS: We conclude that after cesarean section, PCEA with meperidine produces high-quality pain relief with few side effects and has significant advantages over PCIA meperidine. With the caveat that neonatal effects in breast-feeding mothers have yet to be evaluated, it can be highly recommended in this population.

Adult↗
PubMed1996

Epidural meperidine after cesarean section. A dose-response study.

BACKGROUND: Epidural meperidine is effective for postoperative analgesia, but the optimum dose has not been evaluated. METHODS: Five doses of epidural meperidine (12.5, 25, 50, 75, and 100 mg) given at the first request for analgesia after cesarean section were compared. Visual analog pain scores, duration of analgesia as defined by time to first patient-controlled epidural analgesia demand, plasma concentrations of meperidine, side effects, and subsequent 24-h consumption of meperidine were evaluated. RESULTS: All doses were effective, but patients took longer to become pain-free after 12.5 mg (median 30 min) compared with 25 mg (median 12 min, P = 0.038), and duration of analgesia was shorter after 12.5 mg (median 83 min) compared with 25 mg (median 165 min, P = 0.0005). Increasing dose to more than 25 mg did not improve onset or duration of analgesia. Plasma concentrations of meperidine were less than minimum effective analgesia concentration for all doses except 100 mg. There was more frequent nausea (P = 0.004) and dizziness (P = 0.0002) after 100 mg compared with smaller doses. CONCLUSIONS: Epidural meperidine provides effective postoperative analgesia, although of relatively short duration. A single dose of 25 mg is superior to 12.5 mg, but there is no benefit from increasing the dose to 50 mg or greater.

Adult↗
PubMed1997

The cerebral pharmacokinetics of meperidine and alfentanil in conscious sheep.

BACKGROUND: Different opioids have different delays (hysteresis) between their concentrations in blood and their cerebral effects. Possible mechanisms include differences in their rate of penetration into the brain and differences in their distribution volume in the brain. There have been few in vivo studies of the cerebral kinetics of opioids to differentiate these mechanisms. METHODS: The cerebral kinetics of meperidine and alfentanil were examined using conscious sheep that were fitted with long-term monitoring equipment to measure relative changes in cerebral blood flow and opioid concentration gradients across the brain through frequent sampling of arterial and sagittal sinus blood. The data were compared using hybrid physiologic modeling with membrane-limited (consistent with mechanism 1) and flow-limited (consistent with mechanism 2) models of cerebral kinetics. RESULTS: Alfentanil had a variable effect on relative cerebral blood flow, whereas meperidine induced a transient increase. The arteriovenous concentration gradients were small after alfentanil but large after meperidine. The flow-limited model gave acceptable descriptions of observed sagittal sinus concentrations for alfentanil and meperidine, whereas the membrane-limited model collapsed to a flow-limited model. The half-lives of equilibrium between blood and brain were 6.3 and 0.8 min for meperidine and alfentanil, respectively: CONCLUSIONS: The rate of penetration of both opioids into the brain was rapid and not rate-limiting. Large differences in the cerebral distribution volume of meperidine and alfentanil accounted for the respective delays in their peak brain concentration relative to blood.

Alfentanil↗
PubMed1998

A randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate.

BACKGROUND: Combined spinal-epidural (CSE) analgesia produces rapid-onset pain relief and allows ambulation in early labor. Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness. Operative delivery rates might be reduced with CSE, by avoiding or delaying administration of local anesthetics. This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia. METHODS: Healthy parturients at full term were assigned randomly to receive CSE or intravenous meperidine analgesia. The CSE group received 10 microg intrathecal sufentanil, followed by epidural bupivacaine and fentanyl at their next request for analgesia. Parturients receiving intravenous meperidine had 50 mg on demand (maximum, 200 mg in 4 h). Labor and delivery outcomes in both groups were recorded and compared. RESULTS: An intent-to-treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women (CSE, 3.5% vs. intravenous meperidine, 4; P=not significant) or in nulliparous women alone (CSE, 7% vs. intravenous meperidine, 8%; P=not significant). Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients (compared with 0 of 352 who received meperidine; P < 0.01). However, the method of fetal monitoring differed between the two groups. Despite this, neonatal outcomes were similar overall. CONCLUSIONS: Combined spinal-epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term, regardless of parity. However, an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed. Further investigation is warranted.

Adult↗
PubMed1986

The pharmacokinetics of meperidine in acute trauma patients.

Traumatic injury has the potential to alter the hepatic clearance and hence the efficacy and toxicity of drugs by a variety of mechanisms. These include changes in hepatic microsomal enzyme activity, hepatic blood flow rate, and plasma protein binding. Unfortunately, there have been few pharmacokinetic studies in trauma patients. Thus, few data are available to provide guidance in drug regimen design for these individuals. Meperidine clearance was therefore evaluated in patients with traumatic injury and an effort was made to identify physiologic and/or clinical predictors of clearance which could facilitate initial dosage selection. Meperidine total body clearance (TBC) was determined on 12 occasions at steady state following IM administration of meperidine to nine severely injured nonseptic trauma patients with normal renal and hepatic function. TBC of this drug averaged 684 +/- 206 ml/min (mean +/- SD) and was highly correlated with ideal body weight (IBW) (r2 = 0.735; F = 27.75; n = 12; p less than 0.01). The serum concentration of the acute phase reactant protein, alpha 1 acid glycoprotein (AGP), which binds meperidine and many other basic drugs increased strikingly in an apparent linear manner at a rate of 27 mg/dl/day up to 9 days after the traumatic event (r2 = 0.828; F = 42.30; n = 12; p less than 0.01). However, this increase in binding protein concentration was not associated with an alteration in meperidine TBC as has been reported for other drugs. It is concluded that IBW may be a useful guide initial dosage selection of meperidine in acute trauma patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Pharmacokinetic-pharmacodynamic modelling of meperidine in goats (I): Pharmacokinetics.

Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one-compartment open model. In healthy (n = 16) and post-operative (n = 16) goats, the parameters were, respectively: tmax 8.3 +/- 3.9 and 9.2 +/- 5.5 min, Vd 2.763 +/- 1.231 and 3.929 +/- 2.101 l/kg, Clb 0.125 +/- 0.036 and 0.087 +/- 0.025 l/kg/min, Ke 0.0563 +/- 0.0358 and 0.0271 +/- 0.0136 min-1. The plasma profile was best fitted by a two-compartment open model following i.v. injection. In this case, the parameters for healthy (n = 7) and post-operative (n = 13) goats were, respectively: Vd 5.212 +/- 1.992 and 5.085 +/- 2.288 l/kg, Clb 0.096 +/- 0.028 and 0.075 +/- 0.026 l/kg/min, beta 0.0211 +/- 0.0093 and 0.0160 +/- 0.0052 min-1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 +/- 15.8% in healthy (n = 6) goats, but much higher in postoperative (n = 10) ones at 94.6 +/- 30.0%. Meperidine diffused into and out of CSF according to a first-order rate process. The time-course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy (n = 7) and postoperative (n = 13) goats were: elimination rate constant (K(ef)) 0.0269 +/- 0.0131 and 0.0305 +/- 0.0177 min-1, peak CSF concentration time (Tmaxf) 15.9 +/- 5.0 and 17.0 +/- 6.9 min. For the i.v. dosed healthy (n = 6) and postoperative (n = 8) animals, K(ef) was 0.0408 +/- 0.0107, 0.0414 +/- 0.0123 min-1 and Tmaxf was 10.0 +/- 5.0 and 7.7 +/- 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predicted by simple extrapolation from the kinetic data.

Animals↗
PubMed1987

Changes in breathing pattern and chest wall mechanics after benzodiazepines in combination with meperidine.

The effects of repeated sedative i.v. doses of midazolam and diazepam in combination with meperidine on breathing pattern and thoracoabdominal motion were studied in eight healthy male volunteers. At 20-min intervals in a randomized double-blind crossover design the subjects initially received two doses of midazolam 0.05 mg/kg or diazepam 0.15 mg/kg followed by meperidine 0.5 mg/kg and then naloxone 0.4 mg. Breathing pattern and thoracoabdominal motion were measured non-invasively, utilizing a computerized strain gauge technique. The initial injection of both benzodiazepines caused significant decreases in tidal volume, inspiratory time and expiratory time. There were no significant differences between the two drugs in any of these variables. Minute ventilation, mean inspiratory flow and respiratory timing were not significantly affected. The second injection of both benzodiazepines caused only insignificant additional changes. When meperidine was added, the effects on inspiratory time and tidal volume were small and not significant. However, expiratory time increased and was no longer significantly different from control. The injection of naloxone reversed the meperidine-induced changes only, and the breathing pattern was no longer different from that obtained during benzodiazepines alone. The decrease in tidal volume after the benzodiazepines was almost exclusively mediated by a decrease in the abdominal contribution. Additional doses of benzodiazepines did not enhance these changes. However, meperidine caused a further decrease in the abdominal contribution. This decrease was reversed by naloxone. This indicates that the combination of benzodiazepines and meperidine caused a profound decrease in diaphragmatic performance.

Adult↗