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Biomedical subjects

I Kissin

Publications and source records attributed to I Kissin.

At least 19 recordsLinked to original sources
PubMed1996

Ketamine enhances local anesthetic and analgesic effects of bupivacaine by peripheral mechanism: a study in postoperative patients.

Patients with unilateral (n = 14) and bilateral (n = 4) herniorrhaphy participated in this study. With bilateral herniorrhaphy, at the end of the surgery, the wound was infiltrated with a solution of bupivacaine 0.5% and ketamine 0.3% on one side and a solution of bupivacaine 0.5% only, on the other. With unilateral herniorrhaphy, the patients were randomly assigned to one of two groups (n = 7). One group at the end of the surgery received the infiltration with a solution of bupivacaine 0.5% and ketamine 0.3%, the other group received the infiltration with a solution of bupivacaine 0.5% only. The duration of the local anesthetic (response to a von Frey filament) and postoperative analgesic (time to mild spontaneous pain) effects of the infiltrations, as well as wound pain threshold 24 h after surgery (pressure algometry), were determined. In patient with unilateral herniorrhaphy, the addition of ketamine for wound infiltration enhanced the duration of infiltration anesthesia (206 +/- 76 versus 343 +/- 108 min, P < 0.02) and analgesia (240 +/- 45 versus 420 +/- 151 min, P < 0.03). Similar enhancement of the local anesthetic effect was observed in patients with bilateral herniorrhaphy. The increase in pain threshold to pressure on the wound with the addition of ketamine was evident in bilateral herniorrhaphy patients and also with a combination of bilateral and unilateral results (1.39 +/- 0.40 versus 2.35 +/- 0.92 kg, P < 0.02). In the group of five volunteers, the subcutaneous infiltration with 0.3% ketamine produced a local anesthetic effect lasting only 10-20 min. The results indicate that ketamine acting via a peripheral mechanism can profoundly enhance anesthetic and analgesic actions of a local anesthetic administered for infiltration anesthesia.

Analgesics↗
PubMed1996

Alfentanil dose-response relationships for relief of postoperative pain.

The aim of this study was to characterize within-patient alfentanil dose-response curves for the relief of spontaneous postoperative pain and to test the closeness of relationships 1) between pain intensity and alfentanil analgesic requirements, and 2) between alfentanil requirements for analgesic and nonanalgesic (sedative and miotic) effects. The effects of alfentanil were studied in 23 patients after elective abdominal surgery. During a 40- to 60-min testing session, the patient received two intravenous (i.v.) injections of saline (placebo) and up to six 3-micrograms/kg increments of alfentanil at 5-min intervals. The patient rated the pain intensity with a visual analog scale, and in a subgroup of 15 patients the blinded observer rated patients' sedation and measured pupil diameter. Spontaneous postoperative pain was completely relieved in all patients with cumulative doses of alfentanil ranging from 6 to 8 micrograms/kg. The within-patient alfentanil dose-analgesic response curves were primarily quantal in nature: a precipitous decrease in pain intensity (representing > or = 2/3 of the total effect) after the injection of only one of the increments of alfentanil was observed in 15 of 23 patients. When the analgesic effect of alfentanil was presented as the collective response of a group of individuals, the quantal nature of the response was concealed by the wide interindividual variability of the response. No statistically significant relationship was noted between predrug pain intensity and the cumulative dose of alfentanil necessary to produce pain relief. A strong correlation was found between interpatient variabilities in the analgesic and sedative effects of alfentanil (r = 0.75, P < 0.002). At the same time, the relationship between alfentanil requirements for pain relief and that for pupil constriction did not demonstrate any significant correlation. The results suggest that, in a population of patients with postoperative pain, the intensity of spontaneous pain cannot be the primary factor determining the dose of alfentanil necessary for its relief.

Abdomen↗
PubMed1996

Time course characteristics of acute tolerance development to continuously infused alfentanil in rats.

The time course of the development of acute tolerance to alfentanil was characterized in rat experiments using various algorithms of continuous infusion of the drug. To maintain analgesia at a constant level (tail compression test), alfentanil use was steadily increased: Time to 50% increase in alfentanil use was 255 +/- 98 min with analgesia maintained at a level of 50% increase in the pressure threshold, and 203 +/- 116 min with analgesia maintained at a level of 200% increase. With the use of the alfentanil infusion regimen designed to rapidly achieve and maintain the constant alfentanil plasma concentration (120 ng/mL), the rate of development of acute tolerance, measured in terms of time to 50% recovery during continuing infusion, was 81 +/- 26 min with the compression test and 88 +/- 38 min with the hot-plate test, but 374 +/- 46 min with the rotarod test (P < 0.0001). Thus we demonstrated rapid development of acute tolerance to continuously infused alfentanil with different methods of tolerance assessment. The results also indicate that the time course of tolerance development does not depend on the type of noxious stimulation (mechanical versus thermal) if the response is organized predominantly supraspinally, and that acute tolerance to the direct effect of alfentanil on motor functions does not mask the rapid development of tolerance to its analgesic effect.

Alfentanil↗
PubMed1994

Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia.

The aim of this study was to test the hypothesis that the induction and maintenance of anesthesia with the use of fentanyl or ketamine reduces postoperative pain and wound hyperalgesia beyond the period when these effects can be explained by the direct analgesic action of these drugs. Twenty-seven patients scheduled for elective hysterectomy were investigated in a double-blind, randomized study. Patients were divided into three groups. In the fentanyl group, anesthesia was induced with fentanyl 5 micrograms/kg combined with thiopental 3 mg/kg and maintained with isoflurane and fentanyl 0.02 microgram.kg-1.min-1. In the ketamine group, anesthesia was induced with ketamine 2 mg/kg in combination with thiopental 3 mg/kg and maintained with isoflurane and ketamine 20 micrograms.kg-1.min-1. In the control group, anesthesia was induced with thiopental 5 mg/kg and maintained with isoflurane only. Patients in all three groups received identical postoperative pain treatment. The intensity of spontaneous incisional pain and movement-associated pain was measured with a visual analog self-rating method. The surgical wound hyperalgesia was assessed by measuring pain threshold to pressure on the wound by using an algometer, and also by measuring the intensity of pain to suprathreshold pressure on the wound with the visual analog self-rating method. Forty-eight hours after surgery, the pain threshold was 0.90 +/- 0.06 kg in controls, 1.69 +/- 0.19 kg (P < 0.001) in the fentanyl group, and 1.49 +/- 0.15 kg (P < 0.01) in the ketamine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Triple anesthetic combination: propofol-midazolam-alfentanil.

The hypnotic effects of propofol, midazolam, alfentanil, and their binary and triple combinations, were studied in 130 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on verbal command was used as an end-point. Dose-response curves for the three drugs given separately and in combination were determined with a probit procedure and the ED50 values were compared with an isobolographic analysis. The ratios of a single-drug fractional dose (ED50 = 1.0) to a combined fractional dose (in fractions of single-drug ED50 values) indicating the degree of superadditivity (synergism) were: 1.4 (P < 0.05) for propofol-alfentanil, 1.8 (P < 0.0005) for midazolam-propofol, 2.8 (P < 0.0001) for midazolam-alfentanil, and 2.6 (P < 0.0001) for propofol-midazolam-alfentanil. The results indicate that the propofol-midazolam-alfentanil interaction produces a profound hypnotic synergism which is not significantly different from that of the binary midazolam-alfentanil combination.

Adult↗
PubMed1993

Does midazolam inhibit the development of acute tolerance to the analgesic effect of alfentanil?

Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continuous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 micrograms.kg-1.h-1) was given together with midazolam (3 mg.kg-1.h-1), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 micrograms.kg-1.h-1) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg.kg-1) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 micrograms.kg-1) with or without midazolam (3 mg.kg-1) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.

Alfentanil↗
PubMed1993

Tonsillectomy and adenoidectomy pain reduction by local bupivacaine infiltration in children.

Experimental data in humans and animals suggest that during surgery, pain impulses enter the CNS creating a hyperexcitable state in spite of general anesthesia. In a prospective double blind study, pain levels in 22 children undergoing tonsillectomy and adenoidectomy under general anesthesia were compared from day of surgery to Day 10. Patients received pre-incisional infiltration with either bupivacaine (A) or saline (B). Subjective pain was assessed by visual analog scale, and objective pain by deglutition time (100 ml). Subjective constant pain was less (P < 0.05) in group (A) on Day 1: 16 (A) vs. 59 (B) and Day 5: 4 (A) vs. 45 (B). We conclude that local nerve blockade by bupivacaine reduces short- and long-term pain in children undergoing tonsillectomy and adenoidectomy in the presence of general anesthesia.

Adenoidectomy↗
PubMed1993

Pentobarbital-morphine anesthetic interactions in terms of intensity of noxious stimulation required for arousal.

BACKGROUND: Previous reports suggest that the outcome (synergism, antagonism, summation) of opioid-barbiturate interactions may depend on the depth of anesthesia. One aim of the present study was to determine whether pentobarbital, alone and in combination with morphine, blocks awakening caused by noxious stimulation in a dose-related manner: the more intense the noxious stimulation, the more pentobarbital is required to suppress the response. A second aim of the study was to determine whether the pentobarbital-morphine anesthetic interaction depends on the depth of anesthesia measured in terms of intensity of noxious stimulation required for behavioral arousal (recovery of the righting reflex). METHODS: Experiments were performed on rats, with the measure of anesthetic effect being suppression of the righting reflex. The noxious stimulus was pressure on the tail at four levels of intensity: 0.0, 0.25, 2.5, and 3.3 kg, generated with an Analgesy-Meter. Pentobarbital and morphine were injected intravenously via chronically implanted catheters. Dose-response curves for pentobarbital given alone and in combination with morphine were determined (by probit analysis) separately for each of the pressure levels. RESULTS: Pentobarbital, alone and in combination with morphine, blocked awakening caused by noxious stimulation of different intensities in a dose-related fashion so that more anesthetic was required to block awakening with more intense stimulation. The pentobarbital ED50 values were: 12.0, 19.5, 22.7, and 24.3 mg/kg for 0.0, 0.25, 2.5, and 3.3 kg pressure, respectively. The addition of morphine (1 mg/kg) reduced the pentobarbital ED50 values for 0.0, 0.25, and 2.5 kg pressure by 34% (P < 0.0001), 39% (P < 0.0001), and 21% (P < 0.005), respectively. No change was seen in the pentobarbital ED50 value at the maximal (3.3 kg) pressure level. CONCLUSIONS: The results suggest that the depth of anesthesia can be measured in terms of intensity of noxious stimulation required for arousal and that the outcome of barbiturate-opioid anesthetic interaction depends on the depth of anesthesia.

Anesthesia↗
PubMed1993

Barbiturate-benzodiazepine interactions at the gamma-aminobutyric acidA receptor in rat cerebral cortical synaptoneurosomes.

Combinations of benzodiazepines (midazolam and diazepam) with barbiturates (pentobarbital and phenobarbital) exhibit synergistic (supra-additive) hypnotic interactions in rats. Because both benzodiazepines and barbiturates interact with the gamma-aminobutyric acidA (GABAA) receptor complex, we have tested the hypothesis that these supra-additive hypnotic interactions are due to a synergistic effect on Cl- conductance subsequent to binding at allosterically coupled sites on the GABAA receptor ionophore complex. Equilibrium binding and 36Cl- flux measurements were performed under nearly identical conditions using rat brain cerebrocortical synaptoneurosomes. The benzodiazepines and barbiturates alone both allosterically enhance binding of [3H]muscimol to comparable, but modest, extents (range = 18%-32% enhancement). Isobolographic analysis reveals that combinations of benzodiazepines and barbiturates do in fact produce a synergistic enhancement of [3H]muscimol binding. Paradoxically, this effect is not translated into a synergistic enhancement of muscimol-stimulated 36Cl- flux. Because the positively cooperative interactions between benzodiazepines and barbiturates, as demonstrated both behaviorally and by binding measurements, are not reflected in enhanced Cl- conductance, the mechanistic basis for hypnotic synergism may involve other non-GABAergic components.

Animals↗
PubMed1993

Metoclopramide decreases thiopental hypnotic requirements.

We compared the effect of metoclopramide (MCA) with droperidol (DPD) on thiopental hypnotic requirements in 96 unpremedicated female patients. The study was randomized, double-blind, and placebo-controlled. The response to the verbal command was used as an end-point of anesthesia. Two methods of determination of thiopental hypnotic requirements were used: titration (infusion of thiopental at a rate of 0.5 mg.kg-1 x min-1) until the end-point was reached and construction of the dose-response curve based on bolus injections of predetermined doses of thiopental (with the use of probit analysis). The ED50 value of thiopental determined by probit analysis was reduced after the 0.2 mg/kg MCA administration by 44% (P < 0.0001). The thiopental hypnotic requirements obtained with the titration method were as follows: 5.3 +/- 0.3 mg/kg in control, 4.5 +/- 0.2 mg/kg (delta 14%, P < 0.03) with 0.1 mg/kg MCA, 3.2 +/- 0.2 mg/kg (delta 39%, P < 0.0001) with 0.2 mg/kg MCA, and 2.9 +/- 0.2 mg/kg (delta 45%, P < 0.0001) with 0.4 mg/kg MCA. DPD decreased thiopental hypnotic requirements almost to the same degree as MCA, with the ceiling effect observed at doses of 0.01 and 0.02 mg/kg (delta 44%, P < 0.0001). The results indicate that MCA causes a profound decrease in thiopental hypnotic requirements. The similarity between the thiopental sparing effects of MCA and DPD suggests that the blockade of D2 receptors is the main mechanism underlying this effect.

Adolescent↗
PubMed1992

Locomotor activity after recovery from hypnosis: midazolam-morphine versus midazolam.

This study was performed to test the hypothesis that sedation after recovery from pharmacologic hypnosis is less pronounced if hypnosis is induced with a midazolam-morphine combination compared with midazolam administered alone. Loss of the righting reflex was used as an index for the hypnotic effect and reduction of locomotor activity as an index for the sedative effect. One group of rats received midazolam (20 mg/kg i.v) and another group an equipotent (in relation to the hypnotic ef.fect) combination of midazolam (4 mg/kg i.v.) and morphine (1.3 mg/kg i.v.). The duration of loss of the righting reflex in the midazolam and midazolam-morphine groups was 30 +/- 3 and 28 +/- 2 min, respectively (mean +/- SE). The difference between the groups in locomotor activity after recovery from hypnosis was very pronounced. The locomotor activity in the midazolam-morphine group at 1 and 2 h was seven and five times greater, respectively, than in the midazolam group (P < 0.005). The profound difference in locomotor activity for the two treatment groups was explained on the basis of the difference in the outcomes of midazolam-morphine interactions with regard to hypnosis (synergism) and sedation (summation). When the animals recovered from hypnosis, the synergism of the drug interaction ceased to be a contributing factor.

Animals↗
PubMed1992

Anaesthetic interaction between thiopentone and ketamine.

The anaesthetic effect of thiopentone, ketamine and their combinations were studied in 150 patients of ASA Grades I and II. The ability to open eyes on command and purposeful motor response to noxious pressure on the trapezius muscle were used as endpoints of anaesthesia. Dose-response curves for thiopentone, ketamine and their combinations were determined with a probit procedure and compared with isobolographic analysis. The interaction between thiopentone and ketamine was found to be additive for both endpoints of anaesthesia.

Adult↗
PubMed1991

Sedation in the ICU.

The effect of midazolam on the induction dose-response curve for alfentanil was studied in non-premedicated ASA physical status I or II patients. The response to the verbal command was used as an end point of anaesthesia. Dose-response curves for midazolam, alfentanil, and their combination were determined with a probit procedure, and compared with algebraic (fractional) analysis of drug interaction. Interaction between midazolam and alfentanil was found to be synergistic (supra-additive). The results suggest that the use of this combination is advantageous not only because it helps to achieve different anaesthetic goals with specific drugs (a benzodiazepine for unconsciousness and an opioid for blockade of the responses to noxious stimulation), but also because its components are complementary for unconsciousness.

Adolescent↗