Patient flow in the preoperative assessment clinic.

BACKGROUND AND OBJECTIVE: Previous research has shown that a preoperative assessment clinic enhances hospital cost-efficiency. However, the differences in organization of the patient flow have not been analysed. In this descriptive study, we evaluated the consequences of the organization of the patient flow of a preoperative assessment clinic on its performance, by analysing two Dutch university hospitals, which are organized essentially differently. METHODS: In the final analysis, the study included 880 patients who visited either academic centre. The performance of the two preoperative assessment clinics was evaluated by measuring patient flow time, various procedure times and the total waiting time. Patients' age, ASA physical status and any preoperative tests requested by the physician were also recorded. RESULTS: There was a significant difference in patient flow time between the two preoperative assessment clinics. More time was needed for the preoperative assessment when patients' ASA class was higher. The patient flow time was longer when electrocardiogram and venepuncture were performed at the general outpatient laboratory than when they were performed at the preoperative assessment clinic due to longer waiting times. More tests were requested when they were performed at the preoperative assessment clinic. CONCLUSIONS: This study shows that the organization of patient flow is an important aspect of the logistic processes of the preoperative assessment clinic. It might influence patient flow times as well as the number of preoperative tests requested. Together with other aspects of logistic performance, patient satisfaction and quality of medical assessment, patient flow logistics can be used to assess the quality of a preoperative assessment clinic.

Pharmacokinetics of S(+) ketamine derived from target controlled infusion.

BACKGROUND: A computer controlled infusion device for S(+) ketamine was used in combination with a Diprifusor device to provide anaesthesia for 20 ASA I or II patients undergoing elective colonoscopy. The aim of the study was to assess the performance of the pharmacokinetic model for S(+) ketamine used in the delivery algorithm of the device. RESULTS: It was observed that during the first 30 min of infusion there was systematic underprediction by the delivery system of the measured levels of S(+) ketamine. New pharmacokinetic constants were derived from the observed data which provided, on pharmacokinetic simulation, improved prediction of the measured values of S(+) ketamine. Prospective application of this modified model for S(+) ketamine in a further nine study patients was performed and the pharmacokinetic performance of the model was reassessed. The data from all 29 patients was subsequently used to calculate the population distribution of S(+) ketamine clearance. The distribution was found to be normal only in the logarithmic domain. In the normal domain the mode of S(+) ketamine clearance was found to be 35.8 ml kg(-1) min(-1) with 5 and 95% confidence limits of, respectively, 11.5 and 111.1 ml kg(-1) min(-1). CONCLUSION: It was necessary to modify the original published pharmacokinetic parameters incorporated into the S(+) ketamine delivery system in order to simulate improved PK performance during short procedures (<1 h duration) where propofol was concurrently administered. This improved performance was confirmed in a further prospective study.

The use of two continuous glucose sensors during and after surgery.

BACKGROUND: Maintaining plasma glucose between 80 and 120 mg/dL is beneficial for patients admitted to a surgical intensive care unit, but requires frequent glucose monitoring to ensure adequacy of treatment and detection of hypoglycemia. We examined whether continuous glucose sensing is feasible and reliable during and after major surgical procedures using two commercially available sensors. METHODS: Eight patients undergoing abdominal surgery were studied. A CGMS device (Medtronic MiniMed, Northridge, CA) and a GlucoDay device (A. Menarini Diagnostics, Florence, Italy) were placed in the shoulder region, and a second GlucoDay device was placed in the upper leg. Blood glucose was measured every 15 min for a total duration of 12 h. RESULTS: Technical failure of the CGMS was observed peroperatively more frequently than postoperatively (66% of all time points vs. 18%, P < 0.001). Technical failure of the GlucoDay device occurred most frequently in the GlucoDay placed in the upper leg (64% vs. 17%, P < 0.001). Accuracy of all three sensors was comparable peroperatively (74%, 76%, and 63% of values in Zone A of the Clarke error grid for the CGMS, GlucoDay shoulder, and GlucoDay upper leg, respectively, P = 0.2). Postoperatively, better accuracy was observed in both sensors placed in the shoulder compared with the GlucoDay placed in the upper leg (73%, 69%, and 51% of values in Zone A for the CGMS, GlucoDay shoulder, and GlucoDay upper leg, respectively, P < 0.001). CONCLUSIONS: Technical performance and accuracy of continuous glucose sensors need improvement before continuous glucose sensors can be used to monitor strict glycemic control during and after surgery.

Neurohistopathologic findings after a neurolytic celiac plexus block with alcohol in patients with pancreatic cancer pain.

Pancreatic cancer has a very poor prognosis resulting in the death of 98% of patients. Pain may be severe and difficult to treat. Management of pain includes chemotherapy, radiotherapy, pharmacologic treatment, and neurolytic celiac plexus block. Recent reviews of the efficacy of neurolytic celiac plexus block however, have reached conflicting conclusions. In this paper, we present two patients with severe pancreatic cancer pain resistant to pharmacologic treatment. Analgesic effect following repeated neurolytic celiac plexus blocks with alcohol was limited in time. Post-mortem neurohistopathologic examination of the celiac plexus revealed an abnormal celiac architecture with a combination of abnormal neurons with vacuolization and normal looking neuronal structures (ganglionic structures and nerve fibers) embedded in fibrotic hyalinized tissue. Our results show that a neurolytic celiac plexus block with alcohol is capable of partially destroying the celiac plexus. These findings may explain the significant but short-lasting analgesic effect following neurolytic celiac plexus block with alcohol.

Continuous brachial plexus block at the cervical level using a posterior approach in the management of neuropathic cancer pain.

BACKGROUND AND OBJECTIVES: Neuropathic cancer pain due to tumor growth near the brachial plexus is often treated with a combination of nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, and oral or transdermal opioids. We propose placement of a catheter along the brachial plexus using a posterior approach for patients not responding to the above-mentioned treatment. CASE REPORT: We describe 2 patients with neuropathic cancer pain in the arm and shoulder despite treatment with dexamethasone, amitriptyline, gabapentin, opioids, and, in 1 patient, oral ketamine. An increase in daily opioid dosage did not relieve the pain but caused unacceptable side effects of nausea, vomiting, and sedation. Continuous administration of local anesthetics via a brachial plexus catheter inserted at the cervical level using a posterior approach resulted in a markedly improved analgesia and decreased opioid requirement. CONCLUSION: Continuous brachial plexus block should be considered in patients with severe neuropathic cancer pain in the arm and shoulder. To achieve sufficient pain relief for prolonged periods of time, a catheter was inserted to block the brachial plexus using a posterior approach. This technique may be a valuable alternative to the interscalene approach because of the improved fixation of the catheter in the muscle sheet of the trapezius, splenius cervicus, and levator scapulae muscles, and the decreased likelihood of catheter dislodgment during neck movements.

Ethanol and halothane differently modulate HLA class I and class II oligomerization. A new look at the mode of action of anesthetic agents through fluorescence spectroscopy.

The field of research considering the working mechanism of anesthetic agents is a complex one and the site or sites of action of general anesthetics are yet to be elucidated. Through the years, on the molecular level, the discussion has shifted from the lipid theories to the more specific interaction with the proteins responsible for the signal transduction. While this approach led to several models, they offer, at best, partial explanations for the observed phenomena. Anesthetic agents interact with many systems, of which the neuronal is best studied, leaving interaction with the immune defense system relatively unexplored. In this study we focus on the interaction of ethanol and halothane with the co-localization on the membrane of HLA I and II molecules. We show that ethanol tends to randomize the distribution of HLA I and II molecules, while halothane increases the clustering of HLA I proteins. The notion that anesthetics modulate cell function by disrupting clustering and thereby promoting a random distribution is a novel approach that may explain the general involvement of many systems during exposition to anesthetic drugs. In this study we show the disturbance of co-localization of molecules that may form a functional network. The relevance of this finding depends on the importance of these networks for extracellular and intracellular processes.

Neuroprotective effects of riluzole and ketamine during transient spinal cord ischemia in the rabbit.

BACKGROUND: Massive release of central excitatory neurotransmitters is an important initial step in ischemic neuronal injury, and modification of this process may provide neuroprotection. We studied the protective effects of the voltage-dependent sodium channel antagonist riluzole and the N-methyl-d-aspartate receptor antagonist ketamine on hind limb motor function and histopathologic outcome in an experimental model of spinal cord ischemia. METHODS: Temporary spinal cord ischemia was induced by 29 min of infrarenal balloon occlusion of the aorta in 60 anesthetized New Zealand white rabbits. Animals were randomly assigned to one of four treatment groups (n = 15 each): group C, saline (control); group R, riluzole, 8 mg/kg intravenously; group K, ketamine, 55 mg/kg intravenously; group RK, riluzole and ketamine. After reperfusion, riluzole treatment was continued with intraperitoneal infusions. Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after intraperitoneal infusions. Neurologic function, according to Tarlov's criteria, was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated after 72 h. RESULTS: Neurologic outcome was better in groups R and RK than in groups C and K. All animals in group C (100%) and all animals but one in group K (93%) were paraplegic 72 h after the ischemic insult versus 53% in group R and 67% in group RK (P < 0.01 each). More viable motoneurons were present in groups R and RK than in controls (P < 0.05). CONCLUSIONS: The data indicate that treatment with riluzole can increase the tolerance of spinal cord motoneurons to a period of normothermic ischemia. Intraischemic ketamine did not provide neuroprotection in this model.

Nitrous oxide-induced enhancement of gamma-aminobutyric acidA-mediated chloride currents in acutely dissociated hippocampal neurons.

BACKGROUND: Because the synaptic inhibition in the human brain is largely mediated by gamma-aminobutyric acid (GABA), the GABA receptor is of primary interest for the study of the working mechanism of general anesthetics. This article examines the interaction between this type of ion channel and nitrous oxide (N2O). METHODS: Patch clamp recording techniques were applied to investigate the effects of N2O on GABA(A) receptor channels in a whole-cell configuration at room temperature. Acutely dissociated rat hippocampal cells from the CA1 region were used. Rapid application of the agonist muscimol and anesthetics (N2O, pentobarbital, and ethanol) was accomplished using a Y tube application system. Peak chloride (Cl-) currents were measured. RESULTS: Short-term application of muscimol (5-30 microM) with dissolved N2O (80%, approximately 22.5 mM) increased the Cl- current (approximately 140%) compared with muscimol alone. This effect is comparable with results the authors obtained with ethanol (800 mM) and pentobarbital (100 microM). Prolonged exposure (9 min) to N2O further increased Cl- currents by an additional 50%. Concentrations of N2O lower than 12 mM did not show an enhancement of this current, whereas application of N2O alone did not result in any Cl- conductance. CONCLUSIONS: These results indicate that N2O can enhance GABA(A) channel-mediated Cl- currents by modulating the effect of the specific GABA(A) agonist; it is not active by itself.

New and potent inhibitors of nitric oxide synthase reduce motor activity in mice.

Potent inhibitors of nitric oxide synthase (NOS), 3-bromo-7-nitro indazole, 1-(2-trifluoromethylphenyl)imidazole, S-methyl-L-thiocitrulline and 7-nitro indazole, reduced locomotion in mice. These results suggest that activity of NOS and corresponding NO release are of importance for normal locomotion.

Vigilance and EEG power in rats: effects of potent inhibitors of the neuronal nitric oxide synthase.

We examined the effects of potent neuronal nitric oxide synthase inhibitors, 3-bromo-7-nitro indazole (3-Br-7-NI) and S-methyl-L-thiocitrulline (S-Me-TC) on general behaviour, vigilance stages and electroencephalographic (EEG) power spectra in rats. In addition, we studied the effect of 7-nitro indazole (7-NI) on EEG power spectra in rats during dark and light periods. 3-Br-7-NI induced ptosis and decrease of slow wave sleep and rapid eye movement sleep in the rat. 7-NI and 3-Br-7-NI reduced the EEG power density in all frequency bands in the rat, suggesting a depression of central neuronal activity. This effect of 7-NI was more prominent during the day than during the night, indicating a circadian variation in the nitric oxide synthase (NOS) response to NOS inhibitor. EEG power was the most reduced in the 7-9 Hz range of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotion observed following administration of NOS inhibitors. Although S-Me-TC is the most potent NOS inhibitor in vitro experiments, it had less effect on vigilance and EEG power in the rat than other NOS inhibitors used in this study, probably due to its short lasting and blood pressure raising effect. The present results indicate that nitric oxide exerts an excitatory and circadian dependent effect in the central neuronal structures involved in the regulation of vigilance.

Intravenous anaesthetics: some cellular sites of action.

Intravenous anaesthetics have diverse effects on neurones within the central nervous system. Only those that occur at clinical concentrations are likely to be relevant. The dominant effect of many agents is the potentiation of the inhibitory neurotransmitter gamma amino butyric acid (GABA) by various mechanisms while inhibiting the effects of excitatory transmitters seems to be less dominant, except for ketamine.

Anticonvulsant activity of new and potent inhibitors of nitric oxide synthase.

The effects of new and potent NOS inhibitors, S-methyl-L-thiocitrulline (S-Me-TC), 3-bromo 7-nitro indazole (3-Br-7-NI), and 1-(2-trifluoromethylphenyl) imidazole (TRIM), were examined on the pilocarpine-induced seizures in mice. 3-Br-7-NI and TRIM decreased the frequency of status epilepticus and mortality, while TRIM. In addition, significantly reduced the incidence of seizures. The latencies to onsets of seizures, status epilepticus, and mortality were significantly prolonged by all three NOS inhibitors, while duration of seizures was reduced by 3-Br-7-NI and TRIM. These data suggest an excitatory effect of NO in the neuronal structure involved in the pilocarpine-induced seizures.

Visual evoked potentials and nitrous oxide-induced neuronal depression: role for benzodiazepine receptors.

We have examined the role of benzodiazepine receptors in nitrous oxide-induced neuronal depression in rats. The changes in neuronal excitability induced by nitrous oxide and the benzodiazepine inverse agonist, Ro15-4513, were monitored by measurement of visual evoked potentials (VEP). Administration of Ro15-4513 10 mg kg-1 i.p., in rats breathing air, did not affect the amplitude or latency of VEP. However, the same concentrations of Ro15-4513 antagonized nitrous oxide-induced depression of VEP amplitudes. We conclude that antagonism of nitrous oxide-induced depression by Ro15-4513 indicates that at least part of the decreased neuronal excitability caused by nitrous oxide could be ascribed to interactions with the GABAA receptor complex.

Sleep and nitric oxide: effects of 7-nitro indazole, inhibitor of brain nitric oxide synthase.

We examined the effect of 7-nitro indazole (7-NI, 2.5-50 mg/kg, i.p.), an inhibitor of central nitric oxide (NO) synthesis, on general behaviour and sleep. The results show that 7-NI induces ptosis, a loss of the righting reflex and decrease of the EEG amplitudes. Furthermore, a duration of slow wave sleep (SWS) and REM sleep decreased, while the latencies of SWS and REM sleep increased. The effects of 7-NI on general behaviour and sleep were partially antagonized by intraventricular administration of the NO precursor, L-arginine (600 micrograms). These findings indicate that 7-NI induces a state of prominent central depression associated with motor deficit and decrease in sleep stages and wakefulness. It further suggests that NO exerts a significant excitatory effect on the neuronal structure involved in the regulation of locomotion and vigilance.

7-Nitro indazole, an inhibitor of neuronal nitric oxide synthase, attenuates pilocarpine-induced seizures.

7-Nitro indazole (25-100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO) synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced seizures in mice. This indicates that the decreased neuroexcitability of the central nervous system (CNS) following administration of 7-nitro indazole may be due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory and proconvulsant factor in the CNS.

Comparative study of normotensive and hypertensive nitric oxide synthase inhibitors on morphine withdrawal syndrome in rats.

The effects of the normotensive, mainly centrally active nitric oxide synthase (NOS) inhibitor 7-nitro indazole and the hypertensive drug NG-nitro-L-arginine, which blocks both the endothelial and the central NOS, have been examined on naloxone-precipitated withdrawal in morphine-dependent rats. Both drugs attenuated the same withdrawal signs (teeth-chattering, penile licking, diarrhoea, chewing, wet-dog shakes, grooming), while other signs remained unaffected (rearing, jumping, ptosis, rhinorrhoea, irritability on touch). These findings indicate that mainly central (but not endothelial) nitric oxide is involved in the expression of some opioid withdrawal symptoms.

The inhibitory effect of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine.

Norharman (20 mg/kg, i.p.) and ibogaine (40 mg/kg, i.p.) significantly attenuated naloxone (4 mg/kg, i.p.)-precipitated withdrawal syndrome in morphine-dependent rats. Several withdrawal signs, such as teeth-chattering, chewing, penile licking and diarrhoea, were decreased by both norharman and ibogaine. In addition, norharman reduced also the withdrawal grooming and rearing. It is concluded that both norharman and ibogaine are inhibitors of withdrawal syndrome in morphine-dependent rats.

Nitric oxide synthase inhibition reduces wakefulness.

The effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthase and L-arginine, a precursor of NO, was examined on the sleep-waking pattern in rats. L-NMMA (3.75-15 mg/kg, i.p.) reduced wakefulness with a corresponding increase of slow wave sleep and rapid eye movement sleep. The effect of L-NMMA on vigilance was limited to the first hour following drug administration. The effect of L-NMMA was abolished by intracerebroventricular administration of L-arginine (600 micrograms). This indicates that the inhibitory effect of L-NMMA on wakefulness is mediated by decreased NO synthesis and that central NO exerts an excitatory role in vigilance. It further implicates that factors facilitating a release and/or synthesis of NO might lead to increased wakefulness and sleep disturbances.

Behavioral and electrophysiological aspects of nitrous oxide dependence.

We examined the effect of 70% nitrous oxide (N2O) on locomotion and visual-evoked potentials (VEP) in rats. The animals exposed to N2O showed an initial decrease of locomotion, followed by development of tolerance and unaltered motor activity during N2O withdrawal. Similarly, an initial decrease of VEP amplitudes was followed by tolerance to N2O. In addition, some amplitudes (N2-P3, P3-N3, and N3-P4) exceeded the control values, indicating an increase of neuronal excitability of the visual system during a long lasting exposure to N2O. The increase of VEP amplitudes was further potentiated by cessation of this gas. The VEP latencies after initial increase, returned to normal and remained unaltered during N2O withdrawal suggesting that the speed of neurotransmission is not essentially changed during chronic exposure to N2O. However, a significant increase of neuronal excitability during chronic N2O exposure, which further increased by cessation of N2O, could be of clinical importance. Therefore, monitoring of VEP, particularly the amplitude values, may significantly improve a detection of altered neuronal excitability during anaesthesia and drug withdrawal.

Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone-precipitated withdrawal syndrome in morphine-dependent mice.

The effect of intraperitoneally administered nitric oxide (NO) synthase inhibitors has been examined on the naloxone-precipitated withdrawal syndrome in morphine-dependent mice. L-NAME (30-200 mg/kg) and L-NOARG (7.5-50 mg/kg) induced a significant decrease of naloxone-precipitated withdrawal jumping and diarrhoea. However, L-NMMA (3.5-100 mg/kg), considered as a less potent NO synthase inhibitor, did not significantly affect the withdrawal signs in mice. Although a specificity of NO synthase inhibitors is not fully established, these results indicate that inhibition of NO synthesis in the central nervous system and periphery may significantly affect the morphine withdrawal phenomena. Accordingly, this study suggests an involvement of NO in morphine withdrawal syndrome.