Comparative usability of modern anaesthesia ventilators: a human factors study.

BACKGROUND: The anaesthesia ventilator represents the key equipment for intraoperative respiratory care. Improper operation of this device may threaten a patient's health. A self-explanatory interface facilitates handling and decreases the risk of operating errors. This study systematically evaluates the usability of user interfaces in four modern anaesthesia ventilators. METHODS: Twenty naïve operators were asked to execute 20 tasks on each of four different anaesthesia ventilators (Avance CS2™, GE Healthcare; Flow-i™, Maquet; and Perseus™ and Primus™, Dräger) in a randomized order. The success of task execution, frequency of requests for assistance, and processing times were recorded. During the tasks, the operators' visual focus was measured via eye-tracking. Additionally, subjective assessments of usability were evaluated by a standardized questionnaire. For comparison, six experienced operators undertook the same protocol. RESULTS: The overall rate of falsely executed tasks was low. Naïve operators requested assistance least when using the Perseus (26). Pooled processing times were shortest for the Perseus (222 s), followed by the Primus (223 s), the Avance (238 s), and the Flow-i (353 s). Task-specific processing times differed considerably between the devices. Eye-tracking analyses revealed associated interface issues that impeded the operators' performance. Operators rated usability best for the Perseus [mean (sd): 67 (17) arbitrary units] and worst for the Flow-i [50 (16) arbitrary units]. Results from experienced operators support these findings by trend. CONCLUSIONS: The usability of modern anaesthesia ventilators differs considerably. Interface issues of specific tasks impair the operator's efficiency. Eliminating the specific usability issues might improve the operator's performance and, as a consequence, the patient's safety.

Combined paravertebral and intrathecal vs thoracic epidural analgesia for post-thoracotomy pain relief.

BACKGROUND: Although thoracic epidural analgesia (TEA) is considered the gold standard for post-thoracotomy pain relief, thoracic paravertebral block (PVB) and intrathecal opioid (ITO) administration have also been shown to be efficacious. We hypothesized that the combination of PVB and ITO provides analgesia comparable with that of TEA. METHODS: After local ethics committee approval, 84 consecutive patients undergoing open thoracic procedures were randomized to the TEA (ropivacaine 0.2%+sufentanil) or the PVB (ropivacaine 0.5%)+ITO (sufentanil+morphine) group. The primary endpoints were pain intensities at rest and during coughing/movement at 1, 2, 4, 8, 12, 24, 48, and 72 h after operation assessed by visual analogue scale (VAS) score. Data were analysed by multivariate analysis (anova; P<0.05). RESULTS: Patient and surgical characteristics were comparable between the groups. The mean and maximal VAS scores were lower in the TEA (n=43) than in the PVB+ITO group (n=37) at several time points at rest (P<0.026) and during coughing/movement (P<0.021). However, in the PVB+ITO group, the mean VAS scores never exceeded 1.9 and 3.5 at rest and during coughing/movement, respectively; and the maximal differences between the groups (TEA vs PVB+ITO) in the maximal VAS scores were only 1.2 (3.4 vs 4.6) at rest, and 1.3 (4.4 vs 5.7) during coughing/movement. CONCLUSIONS: Although VAS scores were statistically lower in the TEA compared with the PVB+ITO group at some observation points, the differences were small and of questionable clinical relevance. Thus, combined PVB and ITO can be considered a satisfactory alternative to TEA for post-thoracotomy pain relief. ClinicalTrials.gov number. NCT00493909.

Nociceptive and antinociceptive responses to intrathecally administered nicotinic agonists.

Activation of spinal nicotinic receptors evokes a prominent algogenic response. Recently, epibatidine, a potent nicotinic agonist, was found to display an antinociceptive response after systemic administration. To examine the spinal component of this action, effects of three nicotinic agonists epibatidine, cytisine and nicotine--were given intrathecally (IT) and their antinociceptive activity was subsequently assessed. All agents elicited dose-dependent algogenic activity, characterized at lower doses by touch-evoked hyperactivity and at higher doses by intermittent vocalization and marked behavioral activity, with the rank order of potency being epibatidine > cytisine > nicotine. In addition, intrathecal epibatidine elicited a short-lasting, dose-dependent thermal antinociception. In contrast, the other nicotinic agonists at the highest usable dose failed to produce a significant antinociception. Mecamylamine, a nicotinic channel blocker, completely abolished the antinociceptive and algogenic responses of epibatidine. The competitive antagonist, alpha-lobeline, blocked both the analgesic and algogenic responses, but methyllycaconitine inhibited only the algogenic effects of epibatidine. Dihydro-beta-erythroidine, also a competitive antagonist, had no effect on the initial intense algogenic responses. The analgesic response to epibatidine was neither inhibited by naloxone nor by atropine. 2-Amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartate receptor antagonist, did not affect the analgesic response to intrathecal epibatidine or the intense initial algogenic response. Upon repeated administration (30-min interval), epibatidine (1 microg, IT) exhibited marked and rapid desensitization to both the analgesic and algogenic responses which recovered within 8 h. Pretreatment with two consecutive doses of cytisine (5 microg, IT, 30-min apart) inhibited the agitation and analgesic actions of intrathecal epibatidine. Thus, we contend that in addition to the typical nociceptive response elicited by spinal nicotinic agonists, intrathecal epibatidine also exhibits a pronounced but short-lasting antinociception. The analgesic and algogenic responses to intrathecal epibatidine may be mediated by distinct subtypes of spinal nicotinic receptors as suggested by the antagonist studies.

Involuntary transfer as a cause of death and a medical hospitalization in geriatric neuropsychiatric patients.

The effects of mass involuntary transfer on geriatric neuropsychiatric male patients were evaluated by comparing outcomes for three overlapping sets of patients (N = 403, 385, and 378) over several follow-up periods. One group, the "reorganization" sample, consisted of all patients on three geriatric wards at a time just before the wards were reorganized and 20 percent of the patients were transferred to other buildings. The comparison samples comprised two overlapping groups consisting of all patients on the wards four months earlier and four months later.

Effect of isoflurane versus nicardipine on blood flow of lumbar paraspinal muscles during controlled hypotension for spinal surgery.

STUDY DESIGN: This study compared the effects of isoflurane and nicardipine on regional blood flow of the lumbar paraspinal muscles. OBJECTIVES: The purpose of this study was to determine whether treatment with hypotensive agents result in ischemia of the lumbar paraspinal muscles, thereby facilitating surgical procedures. SUMMARY OF BACKGROUND DATA: Despite the general acceptance of controlled hypotension as effective in reducing blood loss during spinal surgery, the changes of blood flow that occur at the lumbar paraspinal muscles when this technique is applied remain unclear. The use of laser Doppler flowmetry allows changes of muscle blood flow to be easily detected in real time with minimal invasion, thereby allowing differences among distinct pharmacological approaches for induction and maintenance of controlled hypotension to be evaluated. METHODS: The prehypotensive and hypotensive (reduction of mean arterial pressure by 20 mm Hg) blood flow of the lumbar paraspinal muscles were assessed with a laser Doppler flowmeter in 40 patients undergoing lumbar spinal surgery. The first half of the patients (n = 20) received isoflurane, whereas the second half received nicardipine to achieve arterial hypotension. RESULTS: Compared with the prehypotensive state, during the hypotensive state, patients in the isoflurane group exhibited a 17% to 46% (mean, 33.7%) decrease in lumbar paraspinal muscle blood flow, whereas patients in the nicardipine group exhibited a 24% to 177% (mean, 82.5%) increase in lumbar paraspinal muscle blood flow. Statistical analysis showed a significant difference in the changes of flux after induced hypotension between the isoflurane and nicardipine group (P < 0.001). CONCLUSIONS: Depending on the pharmacological treatment used to achieve arterial hypotension in spine surgery, there will be either a reduction in paraspinal muscle blood flow (ischemia) or an enhancement of this blood flow (hyperemia).

Failure of prevention against postoperative vomiting by ondansetron or prochlorperazine in patients undergoing gynecological laparoscopy.

BACKGROUND: Ondansetron has been approved for the treatment and prevention of postoperative emesis. Since it is presumably considered to possess potent antiemetic effect with fewer side effects, the administration of ondansetron to inhibit emesis in patients following gynecological laparoscopic surgery might be recommendable. Hence, we examined the effects of intravenous ondansetron at dosage of 4 and 8 mg in comparison with intravenous prochlorperazine at 5 mg and placebo. METHODS: A total of 120 patients were allocated randomly into 3 groups. Group 1 patients who served as control were given NaCl 0.9% 4 mL (placebo) intravenously (i.v.); patients in group 2 and group 3 were given ondansetron 4 mg ondansetron 8 mg i.v. respectively; patients in group 4 were given prochlorperazine 5 mg i.v. Premedication was omitted. RESULTS: Logistic regression analysis adjusted for prognostic factors revealed no significant difference between 5 mg prochlorperazine group and 4 mg or 8 mg ondansetron group as compared over the 24 h study period. CONCLUSIONS: The results of this study suggest that i.v. 4 or 8 mg ondansetron and 5 mg prochlorperazine were not effective in prevention of postoperative emesis in patients undergoing gynecological laparoscopy. Since the cost of ondansetron is high, its routine use for prevention against postoperative nausea and vomiting is not be recommended clinically because of its uncertain benefit.

Assessment of volume preload on uteroplacental blood flow during epidural anaesthesia for Caesarean section.

BACKGROUND AND OBJECTIVE: Epidural and spinal anaesthesia are the preferred mode of anaesthesia for Caesarean section. Volume preloading is recommended to prevent maternal hypotension and a reduction in uteroplacental blood flow, although positive effects of volume preloading on maternal cardiac output and arterial pressure are debatable. Doppler measurements of the umbilical artery beyond deriving pulsatility indices are not routinely performed. METHODS: After Institutional Review Board approval and written informed consent, 14 consecutiVe women with epidural anaesthesia for Caesarean section received either hydroxyethyl starch 500 mL or gelatine 500 mL. Haemodynamic variables monitored were maternal arterial pressure, maximal blood flow velocity and pulsatility indices of the uterine artery derived from Doppler measurements. CONCLUSIONS: Maternal arterial pressure and pulsatility indices in both groups did not change from baseline after intravenous colloid infusion. However, uterine blood flow increased significantly in both groups. The effectiveness of volume preloading may therefore be better described by changes in maximum uterine blood flow velocity than by pulsatility indices or maternal arterial pressure.

Remifentanil for gynaecological and obstetric procedures.

Recently, with the introduction of the novel mu-opioid receptor agonist remifentanil, anaesthesiologists have acquired a unique tool to provide adequate, titratable and predictable analgesia throughout surgery, without the risk of opioid-related delay in postoperative recovery. This new compound will therefore mandate a change in anaesthesia practice from opioid-restricted to opioid-dominated anaesthesia. It is the first in the class of esterase-metabolized opioids within the 4-anilidopiperidine series of drugs, and it possesses an analgesic potency similar to that of fentanyl. The advantages of remifentanil are mainly related to its unique pharmacokinetics, whereas its pharmacodynamics are the same as those of fentanyl. Because of these characteristics, remifentanil-based anaesthesia allows profound opioid analgesia intraoperatively, with rapid and predictable awakening thereafter. Review of the recent literature reveals the potential of remifentanil for improving analgesia in gynaecological procedures and its theoretical advantage in obstetric procedures.

Pharmacological evidence for different alpha 2-adrenergic receptor sites mediating analgesia and sedation in the rat.

Alpha2-adrenergic agonists given intrathecally result in antinociception and intracerebroventricularly (ICV) in sedation. To examine whether different alpha2-adrenergic receptor subtypes differentially mediate antinociception and sedation, we measured the relative potency of three alpha2-adrenergic agonists, dexmedetomidine (DMET), clonidine (CLON) and UK-14.304 (UK), after spinal and ICV administration. Each agonist was given either alone or in the presence of systemically administered yohimbine, which acts as a competitive alpha2-antagonist in unanaesthetized rats. Intrathecal delivery of the agonists alone resulted in a dose-dependent antinociceptive effect (ED50 (nmol): DMET = 1.2, UK = 1.7, CLON = 5.6) with little sedative effect at the lower doses. Yohimbine pretreatment resulted in a rightward shift of the dose-response curves (DMET > CLON > UK). ICV alpha2-adrenergic agonists produced a dose-dependent sedation (ED50 (nmol): DMET = 10.5; UK = 28.7; CLON = 126), with little antinociceptive action. Again, yohimbine pretreatment produced a right shift of the ICV sedation dose-response curves (UK > DMET > CLON). Thus, we conclude that the spinal analgesic effects of DMET, CLON and UK appear to be mediated by two sites. After ICV delivery, DMET, CLON and UK appear to act at a common supra-spinal site to produce sedation and this site resembles that acted upon by UK in the spinal cord.

Comparison of the spinal actions of the mu-opioid remifentanil with alfentanil and morphine in the rat.

BACKGROUND: mu-Opioids administered spinally produce a potent, dose-dependent analgesic response in preclinical and clinical investigations. Side-effect profile of these compounds may be altered as a function of pharmacokinetics. The effects of intrathecal and intraperitoneal remifentanil, an esterase-metabolized mu opioid, alfentanil, and morphine were compared. METHODS: Intrathecal and intraperitoneal remifentanil, alfentanil, and morphine were examined in rats tested for hind-paw thermal withdrawal latency. The antinociceptive response was assessed and in parallel a scoring of four different parameters summarized as a supraspinal index to assess supraspinal side-effect profiles after the several drugs were delivered by the different routes. RESULTS: All opioids produced a dose-dependent analgesic response after intrathecal administration. The ordering of potency (intrathecal ED50 in micrograms) was remifentanil (0.7) > morphine (12.0) > alfentanil (16.3) > GR90291, principal remifentanil metabolite (> 810 micrograms). Time until onset of analgesia after intrathecal or intraperitoneal delivery was morphine > remifentanil = alfentanil. When matched for analgesic effect, the relative duration of action was morphine >> alfentanil > remifentanil. The supraspinal index showed a dose-dependent increase for all agents. All intraperitoneal drugs showed dose-dependent increases in antinociception with potency (intraperitoneal ED50 in micrograms) of remifentanil (4.3) > alfentanil (24.4) > morphine (262). Calculation of intrathecal or intraperitoneal ratios for supraspinal side effects/analgesia (supraspinal index ED50/analgesia ED50) revealed remifentanil to be greatest when intrathecally administered: remifentanil (4 intrathecal: 1.4 intraperitoneal); alfentanil (0.7 intrathecal: 1.5 intraperitoneal); and morphine (1 intrathecal: 5.6 intraperitoneal). CONCLUSIONS: These observations indicate that remifentanil has a powerful spinal opioid action. Consistent with its lipid-solubility, it has an early onset like alfentanil but displays a shorter duration of action after bolus delivery. Despite lipid solubility, remifentanil has a significant spinal therapeutic ratio. These observations likely reflect the rapid inactivation of systemically redistributed agent by plasma esterases.

Continuous intrathecal administration of shortlasting mu opioids remifentanil and alfentanil in the rat.

BACKGROUND: Lipid soluble mu opioids given intrathecally produce a potent, dose-dependent analgesic response, which because of rapid clearance, is of short duration. Such agents delivered by continuous infusion can result in systemic accumulation and significant extraspinally mediated side effects. The effects of intrathecal infusions of two lipid-soluble mu opioids were investigated: remifentanil, an esterase metabolized agent with an inactive metabolite, and alfentanil. METHODS: Rats with chronic lumbar intrathecal catheters received intrathecal infusions (in flow rates of 1.0 microliters/min and 0.1 microliters/min) of remifentanil or alfentanil and were tested for hind paw thermal withdrawal latency, supraspinal side effects (sedation, block of pinna, and corneal responses) and motor impairment. Remifentanil was delivered either in a glycine formulation (R(g)) or in a saline vehicle (R(s)). Separate studies with the glycine vehicle also were undertaken. RESULTS: At an infusion rate of 0.1 microliters/min, remifentanil and alfentanil produced naloxone-reversible, dose-dependent analgesia and supraspinal side effects with the intrathecal ED(50) (micrograms/min; 95% confidence interval) for analgesia: R(s) = 1.5 (1.2-1.8), R(g) = 1.2 (0.7-2.3); alfentanil = 1.5 (1.4-1.6) and for supraspinal side effects: R(s) = 1.7 (1.4-1.9); R(g) = 1.9 (1.6-2.4); alfentanil = 1.5 (1.4-1.7). There was no difference in potency or time until onset for analgesia at either delivery rate (12-20 min), whereas for supraspinal side effects, 1.0 microliters/min resulted in a faster onset for R(g). Recovery of normal thresholds after equianalgesic doses was faster in R(s) than alfentanil and for the supraspinal index faster in R(s) and R(g) groups. R(g), but not R(s), or alfentanil, produced a dose-dependent motor impairment after 90 min of intrathecal infusion at a flow rate of 0.1 microliters/min. Both glycine in R(g) and glycine (matching glycine dose) alone showed parallel time courses for motor impairment and similar intrathecal ED(50) (6.6 vs. 6.4 micrograms/min over 90 min) for this nonnaloxone reversible effect. Intrathecal bolus administration of the same total dose of glycine showed no significant motor effects. CONCLUSIONS: Remifentanil has a rapid onset like alfentanil but shows a faster recovery of action after intrathecal infusion. Despite its rapid clearance, remifentanil induces supraspinal side effects at analgesic effective doses. Moreover, in the current formulation, with glycine, a reversible motor impairment can occur after intrathecal delivery.

The effect of spinal ibuprofen on opioid withdrawal in the rat.

UNLABELLED: This study examines the effect of spinal ibuprofen on the behavioral manifestations associated with the opioid abstinence syndrome. Rats (n = 8 per group) were infused for 5 days with morphine and then pretreated with a spinal bolus dose of ibuprofen before systemic naloxone antagonism (300 microg). Groups included ibuprofen S(+) 1. 36, 13.6, and 136 nmol, and ibuprofen R(-) 136 nmol. A separate group of saline-infused rats was given ibuprofen S(+) 136 nmol before naloxone antagonism. Ibuprofen S(+), but not R(-), dose-dependently and stereospecifically blocked opioid withdrawal hyperalgesia but did not significantly alter other signs of the opioid abstinence syndrome. We conclude that hyperalgesia associated with opioid withdrawal can be blocked by spinally administered ibuprofen, and suggest that there may be a role for spinal prostaglandins in the enhancement of nociception observed in association with the opioid abstinence syndrome. IMPLICATIONS: This study shows that spinal ibuprofen blocks opioid withdrawal hyperalgesia in the rat in a stereospecific fashion, implicating the likely release of spinal prostaglandins during withdrawal and their possible role as neuromodulators in the enhancement of nociception that accompanies this phenomenon.

Effect of continuous spinal remifentanil infusion on behaviour and spinal glutamate release evoked by subcutaneous formalin in the rat.

Injection of formalin into the hind paw of the rat evokes a biphasic nociceptive behavioural response, which is considered to be an animal model of postoperative pain in humans. The initial response (phase 1) is caused by activation of peripheral nociceptors and is followed by a second phase attributed to ongoing activity in primary afferents and increased sensitivity of dorsal horn neurones. The latter effect is thought to result from glutamate-mediated N-methyl-D-aspartate receptor activation. In studies to date it has been difficult to discriminate mechanisms underlying phase 1 and phase 2 events because of the long-lasting half-times of intrathecally administered opioids. To further understanding of the opioid pharmacology of the two different phases of the formalin test, we have studied behavioural activity and spinal glutamate release after intrathecal administration of remifentanil, a new short-lasting mu opioid. Intrathecal remifentanil 3 micrograms microliter-1 min-1 delivered during phase 1 inhibited behavioural response during phase 1 (100%), but did not abolish subsequent phase 2 behavioural activity completely (67 (12) %). Intrathecal remifentanil administered separately in phase 1 and phase 2 revealed a similar ED50 (0.2 microgram microliter-1 min-1) for inhibition of the behavioural responses. In vivo, spinal microdialysis showed incomplete reduction in glutamate concentrations in response to intrathecal remifentanil administration; this in turn inhibited phase 1 behavioural responses. Therefore we contend that supramaximal doses of intrathecal remifentanil sufficient to inhibit phase 1 activity still permitted sufficient glutamate release to allow spinal facilitation. Incomplete suppression of spinal excitatory neurotransmitter release by intrathecal opioids is consistent with spinal wind-up that is triggered during phase 1 and results in phase 2 afferent drive. This might reflect one of the mechanisms underlying post-operative pain.

[Efficacy of oncologic surgery. Does anesthesia influence the postoperative outcome?]. / Effizienz der onkologischen Chirurgie. Hat die Anästhesie einen Einfluss auf das postoperative Ergebnis?

Major surgical interventions in tumour surgery are still associated with perioperative cardiopulmonary, infectious, thromboembolic, cerebral, and gastrointestinal complications. There are different prophylactic and therapeutic possibilities to anticipate or counteract these perioperative complications. The most important, including beta blockers and alpha-2-agonists for patients at coronary risk, preoperative optimisation of oxygen transport in high risk surgical patients and the concept of multimodal perioperative therapy (analgesia, early mobilisation, early enteral nutrition, and others) combined with high perioperative inspiratory oxygen concentration and maintenance of normothermia to reduce wound infection and cardiac complications are described in this paper.

Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery.

BACKGROUND: The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics. METHODS: Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg/kg; maintenance infusion, 0.25 microg x kg(-1) x min-1) or alfentanil (loading dose, 50 microg/kg; maintenance infusion, 1 microg x kg(-1) x min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 microg x kg(-1) min(-1)). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded. RESULTS: Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group. CONCLUSIONS: When both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.

Acute pain management: analysis, implications and consequences after prospective experience with 6349 surgical patients.

An acute pain service (APS) was set up to improve pain management after operation. We attempted to reduce the length of stay in the intensive care unit (ICU) of patients undergoing major surgery and to improve their homeostasis and rehabilitation using a multimodal approach (pain relief, stress reduction, early extubation). Patient-controlled epidural analgesia (PCEA) was a keystone of this approach. If PCEA was not applicable, patients received patient-controlled intravenous analgesia (PCIA) instead. Brachial plexus blockade (BPB) was used for surgery of the upper limbs. A computer based documentation system was used to help evaluate prospectively (a) the quality of analgesia, (b) adverse effects and risks of the special pain management techniques, and (c) cost-effectiveness. Patients receiving PCEA (n = 5.602) received a patient-titrated continuous infusion into the epidural space of either bupivacaine 0.175% or ropivacaine 0.2%, with 1 microg sufentanil mL(-1) added, followed by patient-controlled boluses of 2 mL (lockout time 20 min). For patients receiving PCIA (n = 634) an initial bolus of 7.5-15 mg piritramide was given, and the subsequent bolus was 2 mg (lockout time 10 min). A continuous infusion of bupivacaine 0.25% was administered to patients receiving BPB (n = 113). The dose was titrated to a dynamic visual analogue scale (VAS) scores < 40. The mean treatment periods were: BPB = 4.33 days, PCEA = 5.6 days, PCIA = 5.0 days. In the case of PCEA, the quality of pain relief, vigilance and satisfaction were superior compared with the PCIA method, which resulted in greater sedation and nausea. Although personal supervision was higher for the PCEA-treated patients, cost analysis revealed final savings of Euro 91,620 for the year 1998 obviating the need for an ICU stay totalling 433 days. Provided that PCEA is part of a fast-track protocol employing early tracheal extubation and optimal perioperative management, the associated initial higher costs will be recouped by the benefits to patients of better pain relief after surgery and fewer days subsequently spent in the ITU.

Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy.

BACKGROUND: Recently, the spinal administration of neostigmine was shown to produce a dose-dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra-articular neostigmine after operation in patients undergoing knee arthroscopy. METHODS: Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double-blind manner, after operation 125, 250, or 500 microg intra-articular neostigmine; 2 mg intra-articular morphine; or as control groups intra-articular saline or 500 microg neostigmine given subcutaneously (s.c.). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient-controlled analgesia by morphine, and subsequent 48-h consumption of morphine were evaluated. RESULTS: Intra-articular (500 microg) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra-articular saline and with those given intra-articular morphine. Analgesia lasted longer after 500 microg intra-articular neostigmine (350 +/- 126 min) compared with intra-articular morphine (196 +/- 138 min; P < 0.05) or with the control groups (intra-articular saline, 51 +/- 11 min; s.c. neostigmine, 46 +/- 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra-articular morphine or 500 microg intra-articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra-articular neostigmine. Among all study groups, no adverse effects were observed. CONCLUSIONS: Intra-articular injection of the acetylcholinesterase inhibitor neostigmine produced a moderate but significant analgesic effect. Several mechanisms such as the hyperpolarization of neurons, reduction in the release of pronociceptive neurotransmitters, or activation of the nitric oxide-cyclic guanosine monophosphate pathway might mediate this peripheral cholinergic antinociception by elevating endogenous acetylcholine.

The effects of adding isoproterenol to 0.125% bupivacaine on the quality and duration of epidural analgesia in laboring parturients.

UNLABELLED: This study was conducted to determine the effects of adding isoproterenol to epidural bupivacaine and sufentanil on the quality and duration of analgesia during labor. In a double blind, randomized study, 80 women were divided into two groups, receiving three doses of 0.125% bupivacaine with 7.5 microg of sufentanil and either 12.5 microg of epinephrine (EPI group) or 5 microg of isoproterenol (ISO group). Contraction pain was measured using a 100-mm visual analog scale (VAS) before epidural analgesia, at 5-min intervals for 15 min after each epidural injection, and hourly thereafter. Overall, no significant differences were observed in VAS scores between the groups. However, in the ISO group, VAS scores at 10 and 15 min after the first and second administration were significantly lower than those in the EPI group. Analgesia after each administration lasted significantly longer in patients who received epinephrine. Because of the limited duration of analgesia in the ISO group, more patients in this group received a fourth epidural administration of 0.125% bupivacaine with epinephrine 1:800,000. In conclusion, the addition of isoproterenol to bupivacaine and sufentanil induces a faster onset of analgesia and reduces the duration of analgesia compared with bupivacaine with sufentanil and epinephrine. Therefore, it is preferable to use isoproterenol only once, as a test dose, after the placement of the epidural catheter. IMPLICATIONS: We analyzed the quality and duration of analgesia in laboring women after they received bupivacaine and sufentanil combined with isoproterenol or epinephrine epidurally. We found that the addition of isoproterenol to bupivacaine and sufentanil induces a faster onset of analgesia and reduces the duration of analgesia.

Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic maternal-fetal sheep preparation.

A randomized crossover study was designed using the chronically instrumented pregnant sheep preparation to study the possible effects of epidural injection of adrenaline as a single compound on the circulation of mother and fetus. Three consecutive identical doses of adrenaline were administered epidurally with a 30 min interval between treatments. In a randomized crossover fashion two dosages (10 and 15 micrograms) were tested on different days. The day after the last epidural experiment the same doses of adrenaline were given intravenously (i.v.). Between the two i.v. doses a 30 min interval was allowed for values to return to baseline. Twenty-seven experiments were performed in eight ewes. Epidural administration of adrenaline did not affect maternal mean arterial pressure, maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat rate, or maternal and fetal blood gases and acid-base status. After i.v. administration of adrenaline the uterine blood flow decreased in a dose-dependent fashion, but the other haemodynamic variables were not affected. In conclusion, this study indicates that consecutive epidural injections of adrenaline have no significant effect on maternal and fetal haemodynamic responses, uterine blood flow, blood gases and acid-base status in the gravid ewe. However, an i.v. injection of 10 or 15 micrograms adrenaline decreases the uterine blood flow and could compromise the fetus.

Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model.

UNLABELLED: Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception. The use of intrathecal (i.t.) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether i.t. neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (i.t.) and peripheral (intraarticular; i.a.) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. I.t. neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 microg, 24-28 h: 9.4 microg) and mechanical analgesia (ED50 0-4 h: 3.5 microg, 24-28 h: 4.3 microg). I.t. atropine reversed analgesia by i.t. neostigmine. I.a. neostigmine also resulted in an i.a. atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 microg, 24-28 h: 140.1 microg). Partial suppression of mechanical hyperalgesia was observed after i.a. neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. IMPLICATIONS: This animal study shows that administration of the acetylcholinesterase-inhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain.