Reduction of blood loss using high-dose aprotinin in major orthopaedic surgery.
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Aprotinin↗
Biomedical subjects
R Dirksen
Publications and source records attributed to R Dirksen.
COX 2 selectivity of non-steroidal anti-inflammatory drugs and perioperative blood loss in hip surgery. A randomized comparison of indomethacin and meloxicam.
BACKGROUND: In this prospective randomized study we tested the hypothesis that use of more cyclo-oxygenase 2 (COX 2)-selective non-steroidal anti-inflammatory drugs (NSAIDs) can reduce perioperative blood loss compared with non-selective NSAIDs. METHODS: Data from 200 patients who underwent total hip replacement were studied. Two NSAIDs were compared: indomethacin 50 mg (n = 82) and meloxicam 15 mg (n = 86). Both NSAIDs were given orally 1 h before surgery. RESULTS: The two groups were not different with respect to age, gender, ASA class or duration of surgery. When indomethacin was used preoperatively, intraoperative blood loss was 623 +/- 243 mL (mean +/- SD) and postoperative blood loss 410 +/- 340 mL. After meloxicam, these values were 524 +/- 304 mL and 358 +/- 272 mL, respectively. Total perioperative blood loss after meloxicam was 17% (P < 0.05) less than that observed after indomethacin. CONCLUSION: Perioperative blood loss after meloxicam is less than after indomethacin. These in vivo findings are consistent with in vitro results using selective COX 2 NSAIDs.
Aged↗
Does ibuprofen increase perioperative blood loss during hip arthroplasty?
BACKGROUND AND OBJECTIVE: To determine whether prior exposure of non-steroidal anti-inflammatory drugs increases perioperative blood loss associated with major orthopaedic surgery. METHODS: Fifty patients scheduled for total hip replacement were allocated to two groups (double blind, randomized manner). All patients were pretreated for 2 weeks before surgery: Group 1 with placebo drug, Group 2 with ibuprofen. All patients were injected intrathecally with bupivacaine 20mg plus morphine 0.1 mg, in a total volume of 4 mL, to provide surgical anaesthesia. RESULTS: The presence of severe adverse effects caused eight patients in the ibuprofen group and six in the placebo group to terminate their participation in the trial. The perioperative blood loss increased by 45% in the ibuprofen group compared with placebo. The total (+/-SD) blood loss in the ibuprofen group was 1161 (+/-472) mL versus 796 (+/-337) mL in the placebo group. CONCLUSIONS: Pretreatment with ibuprofen before elective total hip surgery increases the perioperative blood loss significantly. Early discontinuation of non-selective non-steroidal anti-inflammatory drugs is advised.
Analgesics, Non-Narcotic↗
Predictive performance of a physiological model for enflurane closed-circuit anaesthesia: effects of continuous cardiac output measurements and age-related solubility data.
BACKGROUND: The disposition of inhalation anaesthetics is governed by the factors described in the Fick principle. METHODS: We have recalibrated a previously validated physiological model for enflurane closed-circuit inhalation anaesthesia, using individual continuous cardiac output measurements as well as age-related enflurane solubility coefficients as inputs to the model. Two model versions using 'calculated' (Brody's formula) or 'measured' (thoracic electrical bioimpedance) cardiac output values, and two versions with 'standard' (fixed) or 'age-related' solubility coefficients were formulated. RESULTS: Data from 62 ophthalmic surgical patients were used to validate the predictive performance of the four model versions. The root mean squared errors (total error) and scatters (error variation) were similar with the extended model versions, but the group biases (systematic error component) were significantly less with the model versions that included age-related solubility compared with the versions using standard solubility coefficients (bias -0.76/-0.78% vs -3.44/-3.60%). CONCLUSION: The inclusion of age-related solubility coefficients but not of continuous cardiac output measurements improves the predictive performance of the physiological model for closed-circuit inhalation anaesthetic conditions in routine clinical practice.
Adolescent↗
Early assessment of skeletal muscle damage after ischaemia-reperfusion injury using Tc-99m-glucarate.
PURPOSE: After acute arterial obstruction of the lower extremity, muscle damage is the critical determinant for clinical outcome. The extent of muscle damage and limb viability are currently assessed by clinical examination, which is inaccurate. Tc-99m-pyrophosphate (PYP) has been applied for imaging ischaemia-reperfusion damage. More recently, a new imaging agent, Tc-99m-glucarate (GLUC), was introduced for delineating early myocardial infarction after ischaemia-reperfusion. The aim of this study was to determine if GLUC could delineate early skeletal muscle damage after ischaemia-reperfusion. Both tracers were used in a novel murine model of hindlimb ischaemia-reperfusion. METHODS: In anaesthetised mice, ischaemia of one hindlimb was maintained for 2, 3 and 4h using a tourniquet, followed by a reperfusion period of 1h. Additionally, reperfusion periods of 3, 24 and 96h were studied after 3h of ischaemia. PYP or GLUC was injected 45min before end of reperfusion. Concentrations of both agents were determined in blood, reperfused and contralateral muscle. Reperfused-to-contralateral muscle ratios were calculated. In separate experiments, muscle biopsies were obtained for histologic examination. RESULTS: Ischaemia and reperfusion damage was demonstrated histologically. Using scintigraphy GLUC depicted reperfusion significantly better than PYP. After 2, 3 and 4h of ischaemia, the reperfused-to-contralateral ratios for GLUC were 10.7+/-0.9, 8.9+/-0.9 and 8.6+/-1.1, as compared to 4.5+/-0.7, 4.9+/-0.4 and 4.5+/-0.4 for PYP (P<0.05 at all points). For longer periods of reperfusion, the ratios for GLUC decreased to similar levels as observed for PYP. CONCLUSION: The present study indicates that GLUC is a specific early marker of myocyte necrosis after ischaemia-reperfusion. GLUC may become an useful agent for clinical, early, non-invasive monitoring of skeletal muscle damage after ischaemia-reperfusion.
Animals↗
Contractures in skeletal muscle of malignant hyperthermia susceptible patients after in vitro exposure to sevoflurane.
BACKGROUND: Sevoflurane, a potent inhalational anaesthetic agent that is structurally similar to halothane, has some favourable characteristics, but may also be able to trigger malignant hyperthermia (MH) in susceptible patients. The diagnosis of malignant hyperthermia susceptibility relies on the in vitro contracture test on skeletal muscle. The present study was undertaken to investigate whether exposure to sevoflurane of muscles of malignant hyperthermia susceptible (MHS) patients would also cause an abnormal contracture. METHODS: Muscle fascicles obtained from three MHS patients, one malignant hyperthermia non-susceptible (MHN) patient, two control patients and one malignant hyperthermia equivocal (MHE) patient were exposed to sevoflurane instead of halothane in the in vitro contracture test, carried out according to the protocol of the European Malignant Hyperthermia Group. The muscle fascicles were surplus to diagnostic requirements. Sevoflurane concentrations in the testbath were measured using a headspace gas chromatographic technique. RESULTS: The kinetics of sevoflurane concentration in the testbath were similar to those of halothane. An in vitro contracture response of 2 mN or more was seen in all four MHS/MHE patients with sevoflurane but not in the three control/MHN patients. The magnitude of muscle contracture in the sevoflurane test was less than in the conventional halothane test at comparable testbath concentrations. CONCLUSIONS: Sevoflurane can trigger an abnormal contracture in human muscle in vitro. This is indicative of malignant hyperthermia susceptibility. Exposure to sevoflurane should be avoided in patients thought to be susceptible to malignant hyperthermia.
Anesthetics, Inhalation↗
The incidence of transient neurological symptoms after spinal anaesthesia with lidocaine compared to prilocaine.
The purpose of this double-blind study was to investigate the incidence of transient neurological symptoms after the use of isobaric lidocaine and isobaric prilocaine for spinal anaesthesia. Seventy patients (ASA 1-2, age between 18 and 70 years) were randomly assigned to two groups of 35 patients each, to receive either isobaric 2% lidocaine 4 ml or isobaric 2% prilocaine 4 ml intrathecally, at the L3-4 interspace. One patient in the prilocaine group could not be included because data were incomplete. On the first postoperative day, patients were evaluated for transient neurological symptoms. Pain was scored on a 10-point scale. Seven patients (20%) in the lidocaine group had transient neurological symptoms with a mean pain score of 5.3, whereas no patient in the prilocaine group had these complaints (p = 0.006). Symptoms disappeared within 4 days. Prilocaine results in a lower incidence of transient neurological symptoms than lidocaine intrathecally and therefore it is more suitable for short surgical procedures.
Adolescent↗
Itching after intrathecal morphine. Incidence and treatment.
This study was designed to determine whether low doses of intrathecal morphine still result in itching and it evaluates the outcome of a standardized treatment using promethazine and - for intractable itch - naloxone. Patients (n = 143) scheduled for total hip surgery were allocated to four groups (in a double blind manner) with bupivacaine 20 mg in 4 mL but different doses of intrathecal morphine: Group I, 0.025 mg, Group II, 0.05 mg, Group III, 0.1 mg and Group IV, 0.2 mg. The presence or absence of itching was noted every three hours for a 24-h period. When required, standardized treatment was provided. The incidence of itching was: Group I: 14. 3%; Group II: 21.6%; Group III: 48.6%; and, Group IV: 61.7%. Itch was treated by administering promethazine intramuscularly in 2.9% (Group I); 8.1% (Group II); 10.8% (Group III), and 8.9% (Group IV), respectively. Only in group IV there was a single patient who needed naloxone to treat itching. The incidence and severity of itching is a dose-related side-effect in the dose range of 0.025-0.2 mg of intrathecal morphine. Itching still occurs after the low doses of intrathecal morphine, but symptoms vanish after promethazine 25 mg intramuscularly.
Aged↗
Substance P.
Substance P is considered to be an important neuropeptide in nociceptive processes. Although substance P was described more than 60 years ago, there is still controversy about its exact role in nociception. This article reviews the current knowledge about the function of substance P in pain. Special emphasis is put on how to use this knowledge in the development of new ways to treat pain.
Central Nervous System↗
Correlation dimension of the human electroencephalogram corresponds with cognitive load.
This study aimed at assessing the effects of cognitive activity and mental task load on the correlation dimension of the human electroencephalogram (EEG). Three experimental conditions were created: a baseline condition and two cognitive task conditions, a calculation task and a time estimation task. The calculation task was supposed to induce a higher mental load than the time estimation task, which is regarded as a less complex one. This was verified by a subjective rating scale. All conditions differed significantly in subjective estimated task load. The correlation dimension appeared to be higher in both task conditions compared to the baseline condition. A comparison of the two tasks indicated that the difference in correlation dimension between calculation and time estimation was also significant, with the highest value for calculation. It is concluded that cognitive and mental activity is associated with a higher correlation dimension in the EEG. This implies that the correlation dimension is a sensitive parameter in the analysis of electrical brain activity.
Adult↗
A molecular model for the synergic interaction between gamma-aminobutyric acid and general anaesthetics.
Within the context of the discussion about rational polytherapy, we determined the effects of four anaesthetics on the binding of [3H]t-butylbicycloorthobenzoate ([3H]TBOB) to the GABA(A) receptor complex in the presence of several concentrations of GABA (gamma-aminobutyric acid), in order to build a molecular model that can describe and quantify the interactions between the compounds. The empirical isobole method revealed that GABA and the anaesthetics acted synergically in displacing [3H]TBOB. This synergy could be described by a simple molecular model in which both GABA and the anaesthetics displaced [3H]TBOB allosterically and in which GABA allosterically enhanced the binding of the anaesthetics. To get information about the interaction between GABA and anaesthetics, we used [3H]TBOB as a tracer ligand. The model indicated that GABA enhanced the affinity of thiopental 3.0-fold, propofol 5.0-fold, the neuroactive steroids Org 20599 3.5-fold and Org 20549 13-fold. Insight into the molecular mechanism and strength of these interactions can help clinicians to choose therapeutically optimal drug and dose combinations: a step towards rational polytherapy.
Allosteric Site↗
The intensity of preoperative pain is directly correlated with the amount of morphine needed for postoperative analgesia.
UNLABELLED: The aim of this study was to examine whether severity of preoperative pain intensity is related to postoperative pain and morphine consumption. Sixty consecutive patients scheduled for total hip surgery during intrathecal anesthesia were studied. Preoperative visual analog scale (VAS) scores and analgesic intake was assessed 1 day before surgery. Three groups of patients were identified: those with mild pain (n = 12, VAS score 0-4), moderate pain (n = 18, VAS score 4-7), and severe pain (n = 28, VAS score 7-10). Postoperative pain scores were recorded in the first 24 h, as was the amount of morphine delivered by the patient-controlled analgesia pump. There were no differences among the groups in VAS scores at any time. Severe preoperative pain levels correlated with significantly greater postoperative morphine intake. The mean morphine intake during the first 24 h postoperatively was 19.2 mg in the mild pain group, 21.2 mg in the moderate pain group, and 29.5 mg in the severe pain group (P < 0.05 compared with both other groups). We conclude that patients with severe preoperative pain self-medicate to achieve postoperative pain scores equivalent to those of patients with mild and moderate pain and require a greater postoperative morphine intake for adequate analgesia than patients with mild or moderate preoperative pain. IMPLICATIONS: In this study, we showed that severity of preoperative pain intensity relates to postoperative pain levels and morphine consumption. Patients scheduled for total hip surgery with severe preoperative pain require more postoperative morphine in the first 24 h.
Aged↗
Optimization of the dose of intrathecal morphine in total hip surgery: a dose-finding study.
UNLABELLED: We designed this study to determine the optimal intrathecal dose of morphine in total hip surgery. The optimal intrathecal dose was defined as that providing effective analgesia and minimal side effects 24 h after total hip surgery. Patients (n = 143) scheduled for total hip surgery were randomized to four double-blinded groups with a standardized bupivacaine dose but different doses of intrathecal morphine (Group I = 0.025 mg, Group II = 0.05 mg, Group III = 0.1 mg, and Group IV = 0.2 mg). Pain scores, i.v. morphine intake (patient-controlled analgesia), and morphine-related side effects (respiratory depression, postoperative nausea and vomiting, itching, urinary retention) were recorded for 24 h after surgery. Excellent postoperative pain relief was present in all groups. The highest pain scores were found in Group I. The mean use of systemic morphine administered by patient-controlled analgesia infusion pump was 23.7, 17.8, 10.9, and 9.9 mg in Groups I-IV, respectively (P < 0.01 for Groups III and IV versus Group I). We conclude that 0.1 mg of intrathecal morphine is the optimal dose for pain relief after hip surgery with minimal side effects. IMPLICATIONS: Earlier studies showed excellent postoperative pain relief after intrathecal morphine. However, the severity of side effects resulted in decreased enthusiasm for this anesthesia technique. In the present study, we show that an intrathecal dose of 0.1 mg of morphine can be used safely in total hip surgery with excellent postoperative pain relief.
Analgesia↗
Effects of polytherapy compared with monotherapy in antiepileptic drugs: an animal study.
Although monotherapy in epilepsy treatment is frequently advocated, this is not based on studies with equal drug loads. This study was performed to investigate the experimental background of polytherapy with standardized drug loads. Dose-dependent effects on grip strength, accelerod performance, and spontaneous behavior of rats was used to study the effect of combining valproate and ethosuximide. The potency of the drugs (combination) was obtained by fitting the sigmoid Emax equation to the data. Drug interaction was assessed using the isobologram method and quantified by comparing equivalent drug loads with their 95% confidence intervals. We found that the effects of valproate and ethosuximide combine in a simple additive way in the grip strength experiment as well as in the accelerod experiment. In the behavioral studies, however, a higher drug load of the combination was needed to obtain the same amount of sedation, signifying infra-additivity. Infra-additivity of sedative effects is an important finding because this is by far the most frequent side effect mentioned in human studies. However, assessment of the therapeutic effect of the combination will have to be completed before a preference for mono- or polytherapy, based on the balance of adverse effects and efficacy, can be expressed.
Animals↗
Time course of chronic diazepam effects on the auditory evoked potential of the rat.
The time course of chronic diazepam effects on auditory evoked potentials was studied in rats. Auditory evoked potentials were elicited by background and target tones in a passive oddball paradigm. Diazepam was administered by slow release implants to establish constant blood concentrations. Recordings were made during 21 days of treatment and 9 days after treatment ceased. Diazepam increased the amplitude of the P40 component and decreased the amplitude of the P72-P102 components elicited by background tones. Diazepam increased the amplitude of the P40-P48 component and decreased that of the N58 component elicited by target tones. These effects remained constant during treatment. Diazepam further decreased the amplitude of the P102 component elicited by target tones. This effect became more distinct over time. No group differences were found 9 days after treatment. The constant drug effects on middle-latency components (P40-P48) might reflect diazepam-induced changes in sensory information processing. The decreased long-latency component (P102) might reflect a diminished attention to, or discrimination of, target tones. The time course of this effect might reflect diazepam-enhanced habituation.
Animals↗
Selective serotonin reuptake inhibitors may enhance responses to noxious stimulation.
The acute effects of various doses of two selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine) on thermal and electrical stimulation-induced pain were investigated in drug-naive Wistar rats. The hot-plate and the tail-flick test and the noxious-induced withdrawal test were used. The two drugs had no effects on heat-induced pain behavior. However, the two compounds enhanced the motor responses induced by noxious electrical stimulation. These data contrast to what is generally found for tricyclic antidepressants and suggest a modality specific pain system. Cardiac and blood pressure were also found to change, but these changes were not correlated to changes in nociception. Taken together, the data suggest that the acutely administered selective serotonin reuptake inhibitors may exacerbate an acute type of pain.
Animals↗
Effects of early postoperative 5-fluorouracil and ageing on the healing capacity of experimental intestinal anastomoses.
BACKGROUND: Results from a previous study suggested that advanced age does not affect early repair of experimental intestinal anastomoses. The present study aimed to establish whether anastomotic healing is impaired more easily in old animals by immediate postoperative chemotherapy. METHODS: Young adult (2-3 months) and old (27-30 months) rats underwent resection and anastomosis of both ileum and colon. Within each age group, subgroups received intraperitoneal saline or 5-fluorouracil in a dose of 15 or 20 mg per kg per day from the day of operation onwards. After 7 days, anastomotic healing was assessed by wound strength and collagen deposition in the wound area. RESULTS: No differences were found between young and old control groups. The higher dose of fluorouracil induced severe loss of strength with concomitant reduction of wound collagen, which was similar in both age groups (ileum: from 52(13) to 24(8) volume per cent in young animals and from 56(10) to 20(9) volume per cent in old animals; colon: from 58(10) to 37(18) volume per cent in young animals and from 65(5) to 30(17) volume per cent in old animals). The lower dose of fluorouracil induced a significantly greater loss of strength, measured as the bursting pressure, in the old animals (150(49) versus 201(59) mmHg in colon of young rats). CONCLUSION: In this model early anastomotic repair in older animals proceeds normally under optimal conditions, but it is more easily disturbed in the presence of fluorouracil.
Aging↗
Responses to propofol in relation to GABA functionality of discrete parts of the brain of rats.
Genetically-determined regional differences in the GABA-ergic make-up of the brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic general anesthetic. This study compared the responses to propofol in APO-SUS and APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular contractions and oral movements, but a lower incidence of grooming, in APO-SUS rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the behavior marked by both full absence of purposeful movements and by complete loss of righting reflexes, after propofol did not differ between the two lines. APO-SUS rats had less variation of the heart rates and greater variations of diastolic arterial pressures in response to electrical stimulation than the APO-UNSUS rats, and these variations were reduced by increasing doses of propofol. Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol caused a biphasic change in intra-arterial pressures and had the greatest effect in APO-SUS rats. Differences in cerebral GABA transmission, especially in the striato-nigro-collicular pathway, did not give rise to differences in the effect of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these differences in GABA transmission were accompanied by line-specific differences in effect of propofol on certain behavioral and cardiovascular parameters.
Anesthesia, Intravenous↗