Activation of inflammation is the hallmark of pathological processes that follow acute injury. This process is mediated by inflammatory cytokines and adhesion molecules that reside on the surface of endothelium, leucocyte and inflammatory cells. Attenuation of the adhesion cascade has been the subject of several basic science and clinical trials in the management of neurological injury. This review will highlight the role of adhesion molecules in the evolution of secondary injury after cerebral ischaemia and trauma. Potential therapeutic avenues will then be discussed.

Summary

Background and objective: Derived parameters of the electroencephalogram and auditory evoked potentials can be used to determine depth of anaesthesia and sedation. However, it is not known whether any parameter can identify the occurrence of awareness in individual patients. We have compared the performance of bispectral index and a new composite index derived from auditory evoked potentials and the electroencephalogram (AAI 1.61) in predicting consciousness, explicit and implicit memory during moderate sedation with propofol. Methods: Twenty-one patients with spinal anaesthesia received intraoperatively propofol at the age-corrected C50 for loss of consciousness and were presented test words via headphones. Bispectral index and AAI 1.61 (auditory evoked potentials, AEP-Monitor2) were recorded in parallel as well as the Observer's Assessment of Alertness/Sedation-score. Postoperatively, testing for explicit and implicit memory formation was performed. Results: Bispectral index and AAI 1.61 correlated well with loss of consciousness defined by an Observer's Assessment of Alertness/Sedation-score of 2 (identical PK of 0.87), but did not allow a prediction of postoperative explicit or implicit recall. Conclusions: Both bispectral index and AAI may be indices of depth of sedation rather than indicators of memory formation, which persists during propofol sedation even after loss of consciousness.

Summary

Background and objective: The phosphodiesterase-III (PDE-III) inhibitor enoximone-induced marked contractures in skeletal muscle specimens of malignant hyperthermia (MH) susceptible (MHS) human beings and swine. Whether this is a substance specific effect of enoximone or caused by inhibition of PDE-III remained unclear. Therefore, the effects of the PDE-III inhibitor amrinone in porcine MH normal (MHN) and MHS skeletal muscles were investigated.

Methods: MH-trigger-free general anaesthesia was performed in eight MHS and eight MHN swine. The MH status of the swine was determined by detection of the Arg615–Cys point mutation on chromosome 6 indicating MH susceptibility. Skeletal muscle specimens were excised for the in vitro contracture tests with amrinone. Amrinone was added cumulatively every 5 min to muscle specimens in order to obtain organ bath concentrations between 20 and 400 μmol L−1. The in vitro effects of amrinone on muscle contractures and twitches were measured.

Results: Amrinone-induced contractures in all skeletal muscle preparations. MHS muscles developed contractures at significantly lower bath concentrations of amrinone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 80, 100, 150, 200 and 400 μmol L−1 amrinone. Muscle twitches remained unchanged up to and including 200 μmol L−1 amrinone.

Conclusions: Inhibition of PDE-III in general elicited higher contractures in MHS than in MHN muscles. Therefore, a contribution of PDE-III and the cyclic adenosine monophosphate (cAMP) system in the pathophysiology of MH must be suspected.

Summary

Background and objective: The purpose of intraperitoneal local anaesthetic administration is to block visceral nociceptive conduction and to provide an additional route of analgesia. The present study evaluates the effects of sequential injections of bupivacaine on postoperative pain through a subphrenic catheter.

Methods: In this double-blinded controlled study, patients scheduled for gynaecological laparoscopy were randomly divided into two groups. One group received 20 mL of saline with 1 : 200 000 epinephrine through a subphrenic catheter before the incision closure and at 4-hourly intervals for the first postoperative 20 h. The second group received 20 mL of bupivacaine 0.125% with 1 : 200 000 epinephrine at the same injection times. Postoperative pain scores and consumption of analgesics were compared.

Results: There were no statistical differences in pain scores at rest or incidence of shoulder pain between the two groups, but the patients of the bupivacaine group reported lower pain scores on coughing only in the first hour postoperatively (P = 0.007). Although the patients consumed comparable amounts of metamizole and ondansetron, the number of patients requiring supplemental meperidine and flurbiprofen in the bupivacaine group were significantly lower than in the saline group (P < 0.05).

Conclusions: This study demonstrates that intraperitoneal bupivacaine may reduce pain on coughing in the early postoperative period and the consumption of analgesics postoperatively. The subphrenic catheter technique had no impact upon pain at rest and shoulder-tip pain after gynaecological laparoscopy.

Summary

Background and objective: To measure ‘depth of anaesthesia’, anaesthesiologists use a combination of observable end-points such as immobility and autonomic stability. Unconsciousness and amnesia are not reliably observable end-points, but correlate with parameters derived from the electroencephalogram. We investigated the association of subjective assessment and electroencephalographic measures of anaesthetic depth in a group of experienced (>4 yr of experience) and a group of inexperienced (<2 yr of experience) anaesthesiologists. Methods: One hundred ASA I or II patients were assigned to either group. Anaesthesiologists assessed ‘anaesthetic depth’ using an 11-point numeric and a 5-point verbal scale. Bispectral index and spectral entropy were recorded as electroencephalogram parameters. The association between the subjective assessment and the electroencephalogram parameters was calculated using the prediction probability, PK. Results: Association between subjective assessment and electroencephalographic parameters showed a tendency to a better prediction probability in the experienced group. The difference was significant (P < 0.05) for the bispectral index (PK 0.76 ± 0.01 for experienced and 0.71 ± 0.01 for inexperienced anaesthesiologists). In both groups, a large percentage of the data points recorded during surgery showed bispectral index values above the recommended value of 60 (13.2% in the experienced and 34.3% in the inexperienced group) despite a subjective assessment of ‘deep’ or ‘very deep’ anaesthetic depth. Conclusion: The study demonstrates that the association between subjectively assigned values of anaesthetic depth and electroencephalographic parameters of anaesthetic depth is better for anaesthesiologists with more clinical experience. However, in the ‘inexperienced’ as well as ‘experienced’ group a high percentage of bispectral index and entropy values above 60 occurred despite a subjective assessment of adequate anaesthetic depth. Although there was no evidence for explicit memory, this may indicate a risk for memory formation.

Background and objective Increased glutamate concentration in the cerebrospinal fluid has been reported in severely head–injured patients, suggesting that an excessive release of glutamate may be involved in the process of neuronal damage. Ischaemic damage after subdural haematoma has been reported to be reduced by glutamate (N-methyl-D-aspartate: NMDA) receptor antagonists such as dizocilpine and CGS 19755; even though these drugs were given 20–30 min after insult. Excessive release of excitatory amino acids may produce the neural damage after subdural haematoma and NMDA receptor antagonists may become valuable therapeutic drugs. This study compared the effects of ketamine and dizocilpine, on intracranial pressure and histopathological changes after acute subdural haematoma produced by an injection of autologous blood (150 μL) in rats.

Methods The control (n =9), ketamine (n =9) and dizocilpine (n =9) groups, respectively, received saline, ketamine (total dose: 210 mgkg−1) or dizocilpine (total dose: 1.0 mgkg−1) from 0.5 to 8 h after acute subdural haematoma. A silicone group (n =9) had the same volume of silicone injected subdurally.

Results The volume of ischaemic damage in the silicone group (1.3±1.2mm3) was significantly smaller than in the control group (11.9±3.8mm3). Ketamine and dizocilpine did not increase intracranial pressure. Dizocilpine significantly decreased the volume of ischaemic damage (6.1±3.8mm3). Ketamine failed to significantly decrease damage (7.8±5.0mm3).

Conclusions These results suggest that the factors elicited by the clotted blood contribute to the ischaemic damage after subdural haematoma, and that the glutamate receptor antagonist dizocilpine reduces the damage, while ketamine shows only a trend reduction of the damage.

We present a case of accidental epidural administration of potassium chloride, which was diagnosed by clinical signs. The genesis of symptoms and signs following such administration is discussed and compared with other published reports.

We studied the movement response to skin incision in 68 adult (males/females) ASA I–II patients receiving propofol±fentanyl intravenous anaesthesia using the bispectral index and 95% spectral edge frequency monitoring with an A-1050 EEG monitor. Following Ethics Committee approval, patients were randomly assigned to one of the following four treatments: Group P (n=17): propofol infusion, 1 mg kg −1 min−1 intravenous for 2 min, followed by propofol infusion, 200 μg kg−1 min−1, until skin incision; Group PF1 (n=17): fentanyl bolus, 1 μg kg−1 intravenous+ propofol infusion as in Group P; Group PF2 (n=17): fentanyl bolus, 2 μg kg−1 intravenous+ propofol infusion as in Group P; and Group PF3 (n=17): fentanyl bolus, 3 μg kg−1 intravenous+ propofol infusion as in Group P. The bispectral index and 95% spectral edge frequency were monitored continuously and recorded prior to induction of anaesthesia (base-line) and at skin incision. Twelve, 10, 4 and 4 patients responded to skin incision in Groups P, PF1, PF2 and PF3, respectively (P and PF1 vs. PF2 or PF3; P=0.0001, and 0.006). The bispectral index and 95% spectral edge frequency were significantly lower at skin incision compared with the base-line values in all the four treatment groups. However, only bispectral index values were significantly lower in the nonmovement as compared with the movement (M) category (32.6±8.9 vs. 37.4±10.3; P=0.04). Though deeper levels of hypnosis to lower bispectral index and 95% spectral edge frequency values may be effective in preventing the movement response to skin incision, provision of adequate analgesia rather than lower bispectral index and 95% spectral edge frequency (clinical maintenance) values may be more reliable for preventing the response to skin incision as bispectral index and 95% spectral edge frequency measure the hypnotic component of the anaesthetic effect. Lower bispectral index values may be more discriminatory as compared with 95% spectral edge frequency values for preventing the movement response to skin-incision.

Local and systemic immune and haemostatic responses were studied in 10 patients, aged 57–78 years, undergoing elective hip arthroplasty. Cytokines, soluble cytokine receptors, interleukin-1 receptor antagonist, soluble adhesion molecules, antithrombin, fibrin, soluble and fibrin d-dimer were analysed in wound drainage blood and in blood taken from the systemic circulation for up to 24 h post-operatively. Wound drainage blood concentrations of cytokines, interleukin-1 receptor antagonist and soluble cytokine receptors were increased compared with those in the systemic circulation except for the soluble interleukin-6 receptor. In wound drainage blood, soluble tumour necrosis factor receptors (P<0.05), interleukin-1 receptor antagonist (P<0.05) and interleukin-6 (P<0.05–<0.01) increased during the study period. In blood from the systemic circulation interleukin-6 increased (P<0.05) while the soluble interleukin-6 receptor decreased (P<0.05) compared with pre-operative values. Concentrations of soluble adhesion molecules did not change. Wound drainage blood showed marked hypercoagulation. After hip arthroplasty pro-inflammatory cytokines and their inhibitors were mainly confined to the local trauma site. A predominance for inhibitors was noted.

Summary

Background and objective: Opioids and especially fentanyl are widely used during the intensive care unit management of intracranial pressure in fulminant hepatic failure patients as well as during and after liver transplantation. The newer synthetic opioid remifentanil is also increasingly being used in critical care patients. Due to a lack of data relating to the influence of acute hepatic failure on remifentanil and fentanyl pharmacokinetics, this study was designed in order to determine the impact of this condition on the blood levels of these opioids using a pig model. Methods: Twenty pigs were randomly assigned to one of two groups: A group with surgically induced acute hepatic failure by hepatic devascularization (acute hepatic failure, n = 10) and a control group (SHAM, n = 10), subjected to a SHAM operation. Postoperatively, five animals in each group were administered remifentanil (1 μg kg−1 min−1) or fentanyl (0.2 μg kg−1 min−1) by continuous intravenous infusion. Blood samples for determination of drug concentrations were withdrawn at 0 h and 0.5, 1, 5, 7, 9 h after initiation of dosing. Results: Significantly higher blood concentrations were found in animals with acute hepatic failure compared to SHAM-operated animals receiving remifentanil at 5 h (P = 0.003), 7 h (P = 0.007) and 9 h (P = 0.004) and fentanyl at 7 h (P < 0.0005) and 9 h (P = 0.05). The small number and the great variability in drug concentrations did not allow a detailed kinetic analysis to be performed. Approximate clearance values were found to be greater for the SHAM compared with the acute hepatic failure animals for both fentanyl and remifentanil. Conclusions: Hepatic devascularization in our porcine acute hepatic failure model, appears to have significantly altered the disposition of fentanyl and unexpectedly remifentanil. These changes were thought to be brought about by severe disruption of blood flow and biotransformation in the liver, as well as by haemodynamic changes in the acute hepatic failure animals.

Summary

Reporting systems are becoming more widespread in healthcare. Since they may become mandatory under the pressure of insurance companies and administrative organizations, it is important to begin to go beyond a case-by-case approach and to move to a system where there is a general reflection on the best conditions of development and setting up of such systems in medicine. In this paper, we review existing reporting systems, break down their components, examine how they are constructed and propose some ideas on how to articulate them in a dynamic process in order to improve the validity of the tool as mediator of safety, quality and well-being at work.

Patients treated with bleomycin (BLM) are at risk of developing acute respiratory distress syndrome (ARDS) post-operatively, and this has been associated with high intraoperative concentrations of oxygen. We report progressive arterial desaturation noticeable 2 h after the start of a 4-h radical neck dissection for which the anaesthesia included 50% O2 in N2O. The patient had received two courses of bleomycin within the previous 2 months and had undergone an uneventful right hemiglossectomy under shorter but otherwise similar anaesthesia 4 weeks previously. His pulmonary function tests before the second procedure showed a slight depression of diffusing capacity (DLco) to 80% of predicted and minimal airway obstruction consistent with his history of smoking. The pulse oximetric reading during his second procedure reached 75%, but rose to 95% after treatment with methylprednisolone, salbutamol and inspired O2 concentrations between 80% and 100%. By the end of the procedure, he satisfied the criteria for ARDS and was transferred to the ICU, where he developed bilateral pneumonia, deteriorated and died of multiple organ failure. This case suggests that the risk of hyperoxic pulmonary damage in patients exposed to bleomycin may increase not only with the degree and duration of hyperoxia in a given exposure, but also with the latent effects of recent previous exposure. Near normality of pulmonary function tests cannot be taken as reassurance, and small changes may have more adverse prognostic significance than in patients who have not been exposed to bleomycin.

The inhalation of lidocaine attenuates bronchial hyper-reactivity but also causes airway irritation. However, how lidocaine dose and plasma concentration influence relationships are unknown. Accordingly, we evaluated the effects of three concentrations of lidocaine (1, 4, and 10%, total dose of 0.5, 2.0, and 5.0mg kg−1, respectively) vs. placebo in 15 mild asthmatic patients, selected by their response to a histamine challenge (decrease in FEV1 >20% to less than 18mg mL−1 of histamine [PC20]). Baseline lung function, histamine-induced bronchoconstriction, topical anaesthesia, and lidocaine plasma concentrations were obtained. FEV1 following lidocaine inhalation showed the greatest decrease for the highest dose (from 3.79 ± 0.15−3.60 ± 0.15; P=0.0012). Lidocaine inhalation increased baseline PC20 (6.1 ± 1.3mg mL−1) significantly (to 11.8 ± 3.1, 16.1 ± 3.3, and 18.3 ± 4.5mg mL−1, respectively) with no difference between the two highest doses. The duration of local anaesthesia was not significantly different between lidocaine concentrations of 4% and 10%. Thus, lidocaine inhalation, with increasing concentrations of the aerosolized solution, increases initial bronchoconstriction while significant attenuation of bronchial hyper-reactivity is not further enhanced with increasing concentrations from 4 to 10%. Plasma concentrations of lidocaine were always far below the toxic threshold. In conclusion, when local anaesthesia of the airways is required a lidocaine dose of 2.0mg kg−1 as a 4% solution can be recommended for local anaesthesia and attenuation of bronchial hyper-reactivity with the least airway irritation.

Summary

Background and objective: The anaesthesiologist's preoperative interview with the patient is important in preparing the patient for surgery. Its potential protective influence on adverse side-effects from anaesthesia and convalescence is rarely investigated within the context of other perioperative factors. Structural equation modelling allows detection and quantification of all causal relationships and mediator effects in multivariate models. Therefore, this method is presented as a tool and applied to discover the influence of the preoperative interview within socio-demographic variables and duration of surgery on complaints and recovery after anaesthesia.

Methods: The influence of individual satisfaction with the anaesthesiologist's preoperative interview on postoperative events such as nausea/vomiting, difficulties in recovering from anaesthesia, experience of postoperative pain, physical discomfort and satisfaction with convalescence expressed by the patient was analysed by means of structural equation modelling. The variables gender, age and duration of surgery were also included as predictors in the analyses. The model in the total sample of 710 patients was then analysed for structural differences between groups treated either with propofol (n = 204) or with isoflurane + nitrous oxide (n = 267) for maintenance of anaesthesia.

Results: The model revealed that the anaesthesiologist's preoperative interview in combination with associated mediating side-effects explains 45% of the variance of ‘feeling physical discomfort’ and 18% of the variance of ‘satisfaction with convalescence’. The same model could be fitted in the propofol and the isoflurane + nitrous oxide group. Moreover, the structure and the strength of causal relations between variables were identical in the two groups.

Conclusions: The anaesthesiologist's efforts to improve the interview with the patient by more reassuring and proper information will result in less side-effects from anaesthesia and better recovery from surgery. It could be demonstrated that structural equation modelling is a powerful tool for detection of causal relationships and mediator effects in perioperative medicine.

Summary

Background and objective: The cyclic guanosine monophosphate level, which causes an antinociception, is increased in cells as a direct result of phosphodiesterase inhibition. This study used a nociceptive test to examine the nature of the pharmacological interaction between intrathecal zaprinast, a phosphodiesterase inhibitor, and morphine. Methods: Catheters were inserted into the intrathecal space through an incision in the atlantooccipital membrane of male Sprague–Dawley rats. As a nociceptive model, 50 μL of a 5% formalin solution was injected into the hind paw. After observing the effect of zaprinast (37, 111, 369 nmol) and morphine (1, 4, 10, 40 nmol) alone, the interactions of their combination were examined by an isobolographic analysis. Results: Intrathecal zaprinast (P < 0.05) and morphine (P < 0.05) dose-dependently suppressed the flinching observed during phase 1 and phase 2 in the formalin test. The ED50 values (95% confidence intervals) of zaprinast and morphine in phase 1 were 161.9 (87.9–298.3) and 11.6 nmol (4.8–27.9 nmol), respectively. The phase 2 ED50 values (95% confidence intervals) of zaprinast and morphine were 229.9 (142.5–370.9) and 3.9 nmol (1.9–7.6 nmol), respectively. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery a zaprinast–morphine mixture in both phases. The ED50 values of (95% confidence intervals) zaprinast in the combination of zaprinast with morphine in phase 1 and phase 2 were 14.2 (4.9–40.6) and 10.4 nmol (3–35.9 nmol), respectively. Conclusions: Intrathecal zaprinast and morphine are effective against acute pain and facilitated pain state. Zaprinast interacts synergistically with morphine.