[Headache following laparotomy; chronic subdural haematoma following epidural anaesthesia]. / Hoofdpijn na een laparotomie: een chronisch subduraal hematoom na epidurale anesthesie.

A 63-year-old man underwent an exploratory laparotomy because of rectal carcinoma. The operation was performed under general anaesthesia in combination with epidural anaesthesia. Since the operation the patient complained of a headache. Eight weeks after the operation he was hospitalized because of worsening of the headache and also drowsiness. A physical examination showed a slight tendency to incline to the left. A CT scan showed a subdural haematoma, which was relieved with surgery. We suspected that accidental puncture of the dura caused the haematoma. The incidence, causes, symptoms, diagnosis and treatment of this rare complication are discussed.

Is time to peak effect of neuromuscular blocking agents dependent on dose? Testing the concept of buffered diffusion.

BACKGROUND AND OBJECTIVES: For neuromuscular blocking agents, an inverse relationship between potency and time to peak effect has been observed. To test the hypothesis that this relationship is due to buffered diffusion, we investigated the influence of dose on time to peak effect. Pharmacokinetic-pharmacodynamic simulations were performed to support the expected relationships between potency, dose, peak effect and time to peak effect. METHODS: Pigs (20-28 kg body weight) were anaesthetized with ketamine and midazolam, followed by pentobarbital and fentanyl intravenously. Neuromuscular block was measured by stimulating the peroneal nerve supramaximally at 0.1 Hz and measuring the response of the tibialis anterior muscle mechanomyographically. After an initial dose to establish the individual ED90 of a neuromuscular blocking agent (rocuronium, vecuronium, pipecuronium or d-tubocurarine), five different doses of the same compound were administered to each animal, aiming at 20%, 40%, 60%, 75% or 90% block, in a random order. Doses were given 45 min after complete recovery of the twitch response. RESULTS: For rocuronium and pipecuronium, time to peak effect increased with dose, whereas dose did not affect time to peak effect of vecuronium and d-tubocurarine. Simulations predict that time to peak effect decreases with dose if buffered diffusion is taken into account. CONCLUSIONS: The results suggest that buffered diffusion does not play a dominant role in the time to peak effect of neuromuscular blocking agents. Therefore it is unlikely that the observed inverse relationship between potency and time to peak effect of neuromuscular blocking agents in the clinical range is due to buffered diffusion.

Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study.

BACKGROUND: Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia as a consequence of a neuropathic pain syndrome, by means of correlating subjective pain scores with pain thresholds obtained with quantitative sensory testing. METHODS: During a 4-week trial, we administered a cannabis extract to 17 patients with allodynia. We quantified the severity of the allodynia with Von Frey monofilaments before, during and after the patients finished the trial. We also asked the patients to rate their pain on a numeric rating scale at these three moments. RESULTS: We found that most of the effect of the cannabis occurred in the last 2 weeks of the trial. In this phase, we observed that the pain thresholds, as measured with Von Frey monofilaments, were inversely correlated with a decrease of the perceived pain intensity. CONCLUSION: These preliminary findings indicate clinical relevance of quantitative sensory testing with Von Frey monofilaments in the quantification of allodynia in patients with neuropathic pain, although confirmation of our data is still required in further studies to position this method of quantitative sensory testing as a valuable tool, for example, in the evaluation of therapeutic interventions for neuropathic pain.

Decreased number of acetylcholine receptors is the mechanism that alters the time course of muscle relaxants in myasthenia gravis: a study in a rat model.

BACKGROUND: In myasthenic patients, the time course of action of non-depolarizing neuromuscular blocking agents is prolonged and the sensitivity is increased. We used our antegrade perfused rat peroneal nerve anterior tibialis muscle model to investigate if this altered time course of effect and sensitivity can be explained by the decreased acetylcholine receptor concentration that is caused by the disease. METHODS: Functional acetylcholine receptors were reduced by administration of alpha-bungarotoxin or by injecting monoclonal antibodies against rat acetylcholine receptors (experimental autoimmune myasthenia gravis). After induction of anaesthesia, the model was set up and perfusion of the tibialis anterior muscle with blood was started. After stabilization of the twitch, rocuronium or pancuronium were infused until 90% block was obtained. Twitch data and infusion data were recorded and used to calculate the time course of effect and potency. RESULTS: The potency of neuromuscular blocking agents was increased and the offset of the neuromuscular block was prolonged in both the alpha-bungarotoxin groups and the experimental autoimmune myasthenia gravis groups compared to controls. CONCLUSION: This study shows that the increased sensitivity to neuromuscular-blocking agents in myasthenia gravis can be accounted for by a decreased number of acetylcholine receptors. It also shows that the antegrade perfused rat peroneal nerve anterior tibialis muscle model is a suitable model to study the effects of myasthenia gravis on the time course of effect of neuromuscular blocking agents.

Model to describe the degree of twitch potentiation during neuromuscular monitoring.

BACKGROUND: Neuromuscular block is estimated by comparing the evoked peak twitch with a control value measured in the absence of neuromuscular block. In practice, this control value is often difficult to determine because repeated motor nerve stimulation enhances the evoked mechanical response of the corresponding muscle, resulting in an increased twitch response. This is known as twitch potentiation or the staircase phenomenon. It is probably the result of myosin light chain phosphorylation creating an increased twitch force for a given amount of Ca(2+) released at each action potential. Modelling of potentiation may improve studies of neuromuscular blocking agents using mechanomyography or accelerometry. METHODS: We used one- and two-exponential models to describe the degree of myosin light chain phosphorylation and associated twitch potentiation. These models were fitted to accelerographic twitch force measurements for various stimulation patterns and frequencies used in neuromuscular monitoring. RESULTS: Fitting a two-exponential model to twitch data for various stimulation rates and patterns provides better prediction than a one-exponential model. A one-exponential model performs poorly when the stimulation rate varies during measurement. CONCLUSIONS: We conclude that a two-exponential model can predict the degree of twitch potentiation for the stimulation patterns and frequencies tested more accurately than a one-exponential model. However, if only one stimulation frequency is used, a one-exponential model can provide good accuracy. We illustrate that such a potentiation model can improve the ability of pharmacodynamic-pharmacokinetic neuromuscular block models to predict twitch response in the presence of a neuromuscular blocking agent.

Biphasic EEG changes in relation to loss of consciousness during induction with thiopental, propofol, etomidate, midazolam or sevoflurane.

The time course of four EEG effect variables, amplitude in the 2-5 Hz and in the 11-15 Hz band, spectral edge frequency 95% (SEF95), and bispectral index (BIS), in response to increasing concentrations of thiopental, propofol, etomidate, midazolam, or sevoflurane during a 10 min induction of anaesthesia was studied in 25 patients to determine the existence of a biphasic effect and to study the relationship of the EEG effect to the moment of loss of consciousness. A biphasic effect, that is, an initial increase of the effect variable followed by a decrease at higher concentrations, during the transition from consciousness to unconsciousness was found in EEG amplitude (both frequency bands) and in SEF95 for all anaesthetics except midazolam. There was a concentration-related decrease in BIS for all anaesthetics. There was no consistent relationship between the time of occurrence of the peak EEG effect, or the value of the EEG variable and the moment of loss of consciousness. With rapidly changing drug concentrations during the induction of anaesthesia, none of these EEG effect variables could be correlated to the moment of loss of consciousness.

Predictability of processed electroencephalography effects on the basis of pharmacokinetic-pharmacodynamic modeling during repeated propofol infusions in patients with extradural analgesia.

BACKGROUND: Pharmacokinetic-pharmacodynamic (PKPD) modeling can be used to characterize the concentration-effect relation of drugs. If the concentration-effect relation of a hypnotic drug is stable over time, an effect parameter derived from the processed electroencephalographic signal may be used to control the infusion for hypnosis. Therefore, the stability of the propofol concentration-electroencephalographic effect relation over time was investigated under non-steady state conditions. METHODS: Three propofol infusions (25 mg x kg(-1) x h(-1) for 10 min, 22 mg x kg(-1) x h(-1) for 10 min, and 12.5 mg x kg(-1) x h(-1) for 20 min) were administered to 10 patients during extradural analgesia. Each successive infusion was started immediately after the patient had regained responsiveness after termination of the preceding infusion. Electroencephalography was recorded from bilateral prefrontal to mastoid leads. Electroencephalographic amplitude in the 11- to 15-Hz band and the Bispectral Index were used as electroencephalographic effect variables. PKPD parameters were calculated with use of parametric and nonparametric models based on electroencephalographic data and arterial propofol concentrations derived during the initial infusion, and these were used to predict electroencephalographic effect during the subsequent infusions. The predictability of the electroencephalographic effects was determined by the coefficient of determination (R2) and of the -2 log likelihood of the sequential infusions. RESULTS: The direction of electroencephalographic changes in response to the infusions was reproducible. Although PKPD parameters could be estimated well during the initial infusion (median [range] parametric R2 = 0.74 [0.56-0.95] for electroencephalographic amplitude and 0.90 [0.27-0.99] for Bispectral Index), none of the modeling techniques could predict accurately the electroencephalographic effect during subsequent infusions (R2 = 0.00 [-0.31-0.46] for electroencephalographic amplitude and 0.15 [-.46-0.57] for Bispectral Index; P < 0.01). CONCLUSIONS: The relation between blood propofol concentrations and the electroencephalographic effect under non-steady state conditions is not stable over time and is too complex to be modeled by any of the applied PKPD models.

A practical clinical approach to management of the difficult airway.

Difficult airway management represents a challenge in anaesthesia. In the last decades airway difficulty awareness has improved as a result of better anticipation and decision-making. Airway algorithms and protocols have a more prominent role in training and in clinical anaesthesia practice. In addition, several new instruments and therefore new techniques have been developed. These have improved possibilities for the clinician to secure the airway. Clinicians should become familiar with this equipment and techniques by using them on a regular basis in elective cases. The instruments available must be selected by the characteristics of the patient population, the local circumstances and the experience of the anaesthesiologist. The aim of this paper is to provide some practical guidelines with respect to airway difficulty predictors and airway instrument choice.

Urinary, biliary and faecal excretion of rocuronium in humans.

The excretion of rocuronium and its potential metabolites was studied in 38 anaesthetized patients, ASA I-III and 21-69 yr old. Rocuronium bromide was administered as an i.v. bolus dose of 0.3 or 0.9 mg kg-1. In Part A of the study, the excretion into urine and bile, and the liver content were studied. Plasma kinetics (n = 19) were similar to those reported previously. Urinary recovery within 48 h after administration was 26 (8)% (mean (SD)) (n = 8) of the dose. In bile obtained from T-drains, the recovery within 48 h was 7 (6)% (n = 11). The rocuronium concentration in bile declined bi-exponentially, with half-lives of 2.3 (0.7) and 16 (11) h respectively (n = 6). In three patients from whom stoma fluid was collected, the amount of rocuronium recovered ranged from 0.04 to 12.0% of the dose. In liver tissue obtained from four patients undergoing hemihepatectomy, the estimated amount of rocuronium at 2-5 h after administration ranged between 6.3 and 13.2% (n = 4). In the second part of the study (Part B), urine and faeces were collected over 4-8 days and the recovery was 27 (13)% and 31 (23)% of the dose respectively (n = 10). In most samples, irrespective of the type of biological material, only small amounts of the metabolite 17-desacetyl-rocuronium was found. The results demonstrate that rocuronium is taken up by the liver and excreted into bile in high concentrations. The faecal and urinary excretion of unchanged rocuronium are the major routes of rocuronium elimination.

Rapacuronium 2.0 or 2.5 mg kg-1 for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg-1.

The purpose of this nine-centre study in 602 patients was to show that the frequency of acceptable intubating conditions after rapacuronium 2.0 or 2.5 mg kg-1 is not more than 10% lower than the frequency after succinylcholine 1.0 mg kg-1 during rapid-sequence induction of anaesthesia with fentanyl 1-2 micrograms kg-1 and thiopental 2-7 mg kg-1. Laryngoscopy and intubation were carried out 60 s after administration of muscle relaxant by an anaesthetist blinded to its identity. Intubating conditions were clinically acceptable (excellent or good) in 91.8% of patients given succinylcholine and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg-1 respectively. With respect to the percentage of clinically acceptable intubating conditions, the estimated difference (and the upper limit of the one-sided 97.5% confidence interval) between succinylcholine and rapacuronium 2.0 mg kg-1 was 7.8 (14.4)% and between succinylcholine and rapacuronium 2.5 mg kg-1 it was 4.0 (10.2)%. For both comparisons, the upper limit of the one-sided confidence interval exceeded the predefined 10% difference. Hence, it could not be demonstrated that the intubating conditions with either of the two doses of rapacuronium were not inferior to those with succinylcholine 1.0 mg kg-1. The increase in heart rate was significantly greater during the first 5 min in the rapacuronium groups, but the arterial pressure increased significantly only in the succinylcholine group (P < 0.001). Respiratory side-effects were observed in 4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium 2.0 and 2.5 mg kg-1 respectively (P < 0.05). As the non-inferiority of intubating conditions after rapacuronium 2.0 and 2.5 mg kg-1 could not be proven, succinylcholine should be considered the neuromuscular blocking agent that provides better intubating conditions for rapid-sequence induction.

Structure-pharmacokinetics relationship of series of aminosteroidal neuromuscular blocking agents in the cat.

To obtain more insight in the relationship between physicochemical properties of neuromuscular blocking agents (NMBAs) and their pharmacokinetic characteristics, a series of 12 aminosteroidal NMBAs, supplemented with data on five related NMBAs from the literature, was investigated in anaesthetized cats. After i.v. bolus injection, plasma concentration decreased very rapidly, showing a biphasic pattern, with half-lives ranging from 0.4 to 1.4 min, and from 3 to 10 min, respectively. Clearance was in the range from 24 to 58 ml. min(-1). kg(-1). Compounds containing an acetyl-ester group at position 3 were partly metabolized to the 3-OH derivative. The urinary excretion of the parent drug and metabolites amounted to <10% for each of the compounds. The parent drugs were excreted in large amounts into bile, along with smaller amounts of 3-OH derivatives. The terminal half-life of the urinary and biliary excretion rate were markedly longer than the apparent terminal half-life in plasma, ranging from 11 to 40 min, and from 119 to 489 min in urine and bile, respectively. Lipophilicity of the NMBAs, expressed as the partition coefficient octanol/Krebs (log P), was found to be correlated positively with unbound plasma clearance and unbound initial plasma clearance, and negatively with plasma half-life, volume of distribution at steady state, and mean residence time. The increase of the unbound plasma clearance with increasing lipophilicity is counteracted by the concurrent increase in plasma protein binding.

Rapacuronium.

Rapacuronium (Org 9487; ED90 = 1 mg x kg(-1)) is a new, low potency, short-acting, non-depolarizing neuromuscular blocking agent. An intubating dose of 1.5xED90 or 1.5 mg x kg(-1) of rapacuronium offers acceptable intubating conditions within 60-90 s in most patients. A complete block from this dose can be reversed immediately with satisfactory recovery in 12-16 min. Side-effects are dose-related and are mainly haemodynamic, i.e. an increase in heart rate and a decrease in blood pressure.

The relationship between rate of administration of an intubating dose of rocuronium and time to 50% and 90% block at the adductor pollicis muscle.

OBJECTIVE: To determine the relationship between the rate of rocuronium injection and the onset time of neuromuscular block. METHODS: After intravenous induction, 60 female patients (ASA I-II) were assigned randomly into 3 groups for rocuronium administration within 1-15, 15-30 or 30-60 seconds. Acceleromyography of the thumb was performed using train-of-four (TOF) stimulation. Times to 50% and 90% twitch depression of the first twitch of the TOF stimulation (T1) were recorded. RESULTS: Injection time significantly influences time to 50% relaxation, but not time to 90% relaxation. Body mass index is negatively correlated with time to 50% and 90% relaxation. CONCLUSIONS: We conclude that rate of injection influences only the initial phase of development of the block and that slower injection times do not significantly affect time to 90% relaxation at the adductor pollicis muscle.

The effect of single twitch and train-of-four stimulation on twitch forces during stable neuromuscular block.

OBJECTIVE: We investigated whether the response to a single twitch (ST) stimulus or the first response (T1) to a train-of-four (TOF; 4 stimuli at 2 Hz) stimulus following a stimulus interval of 10 s (i.e., the time between two consecutive ST or TOF stimuli) is influenced by the preceding stimulus in the presence of a stable 50% neuromuscular block. In addition, we determined whether ST and TOF stimulation yield different results under these circumstances. METHODS: Twitch forces were measured in both tibialis anterior muscles of six cats. In the presence of a stable 50% neuromuscular block the stimulation pattern (ST or TOF) or stimulus interval (3.3, 10 or 30 s) was varied every 30 min. A linear mixed model was used for statistical analysis. RESULTS: ST forces with a stimulus interval of 3.3 s were 10.3% (95% CI: 7.3-13.3%) smaller than those with a stimulus interval of 10 s. For T1 forces this effect was 15.2% (95% CI: 12-18.4%). There was no significant difference between twitch forces with stimulus intervals of 30 and 10 s. For a stimulus interval of 3.3 s the ST forces exceeded the T1 forces by 7.6% (95% CI: 4.4-10.8%); no significant differences were found between the ST and T1 forces for stimulus intervals of 10 and 30 s. CONCLUSIONS: The ST or T1 force during stimulation with a stimulus interval of 10 s or more during a stable 50% neuromuscular block in the tibialis anterior muscle of the cat is not affected by the preceding stimulus. In addition, ST and T1 forces do not differ when employing a stimulus interval of 10 s or more under these circumstances. Our results thus indicate that the known differences between ST and T1 forces after a bolus injection of a muscle relaxant can not be explained by differences in acetylcholine release when the stimulus interval exceeds 10 s.

Transient nerve damage following intubation for trans-sphenoidal hypophysectomy.

PURPOSE: To describe a case of transient lingual and hypoglossal nerve damage following intubation for a trans-sphenoidal hypophysectomy. CLINICAL FEATURES: A 56-yr-old acromegalic man was scheduled for trans-sphenoidal hypophysectomy. He had been treated with octreotide six months previously which had reduced the swelling of the tongue to an acceptable degree to the patient. During the anesthetic procedure there were no problems. The intubation was performed without any difficulty, no force had been used to place the endotracheal tube, a throat pack was inserted and, before extubation, an oro-gastric tube was inserted. Three days after surgery the patient complained of numbness and swelling of the left side of the tongue, he had difficulty in moving the tongue, speaking difficulties and problems in swallowing food were noted. Also taste was lost on this side of the tongue. Left lingual and hypoglossal nerve damage was diagnosed, which was confirmed by the neurologist. After four months of intensive physiotherapy and speech therapy, the symptoms disappeared. CONCLUSION: This is a report of a very rare complication of lingual and hypoglossal nerve damage in an acromegalic patient. This incident suggests forceful laryngoscopy, hyperextension of the head and the throat pack (tightly packed in the oropharynx) can result in injury of the lingual and the hypoglossal nerves.