Summary

Background and objective: Since the moribund hypodynamic phase of septic shock has primarily been studied in small animal models, the objective of this study was to investigate the usefulness of infusing Salmonella typhosa endotoxin at incrementing doses to establish an ovine model of hypodynamic endotoxaemia.

Methods: In a prospective laboratory experiment, eight adult ewes were instrumented for a chronic study. Following a baseline measurement in the healthy state, a continuous endotoxin infusion was started with 10 ng kg−1 min−1 and was doubled every hour seven times. Haemodynamics, key variables of oxygen transport, and arterial lactate concentrations were determined every hour.

Results: In a dose-dependent manner, endotoxin infusion caused pulmonary hypertension, decreased cardiac output and mean arterial pressure, increased heart rate, and to a certain extent, systemic vascular resistance index. Following 4 h of endotoxaemia, the maximum decrease in cardiac output occurred (4.8 ± 0.2 vs. 7.6 ± 0.3L min−1; P < 0.001). This was accompanied by tissue dysoxia, represented by decreases in oxygen delivery (797 ± 20 vs. 1041 ± 28 mL min−1), oxygen consumption (277 ± 14 vs. 396 ± 15 mL min−1) and oxygen extraction rate (0.35 ± 0.01 vs. 0.38 ± 0.01%; each P < 0.01), as well as an increase in arterial lactate concentration (1.7 ± 0.1 vs. 0.7 ± 0.1 mmol L−1; P < 0.05).

Conclusions: This large animal model may be helpful to study the pathophysiology responsible for cardiovascular failure, and also new therapeutic approaches relevant to management of hypodynamic circulation in the common setting of progressed systemic inflammation.

Summary

Background and objective: The beta-adrenergic blocker esmolol and the alpha 2-adrenergic agonist dexmedetomidine have the potential to decrease perioperative myocardial ischaemia. The pathophysiological mechanisms involved in these anti-ischaemic properties have not been thoroughly studied. We compared the effects of esmolol and dexmedetomidine on two indices of overall myocardial oxygen demand and on directly measured myocardial oxygen consumption of the left anterior coronary artery territory.

Methods: Eleven mongrel dogs were instrumented to measure aortic and left ventricular pressure, aortic and left anterior coronary artery flow and myocardial wall thickening. Variables related to myocardial oxygen metabolism were also determined. Measurements were performed during four sequential experimental conditions in each dog (Control 1: esmolol; Control 2: dexmedetomidine).

Results: Esmolol and dexmedetomidine decreased haemodynamic indices of myocardial oxygen demand to a similar extent: esmolol decreased the rate–pressure product by 16 ± 3% and the pressure–work index (PWI) by 16 ± 3%, dexmedetomidine decreased the rate–pressure product by 26 ± 3% and the PWI by 16 ± 7%. However, these similar decreases resulted from different haemodynamic effects of the two study drugs. Dexmedetomidine had a more pronounced bradycardic effect than esmolol (P = 0.01) and increased systolic aortic pressure (SAP) by 15 ± 4% while esmolol decreased SAP by 8 ± 2% (P < 0.01). dP/dtmax and regional myocardial area decrease were lower after esmolol than after dexmedetomidine. Neither drug had an effect on myocardial oxygen consumption.

Conclusions: Esmolol and dexmedetomidine decreased two haemodynamic indices of overall myocardial oxygen demand to a similar extent but neither drug decreased directly measured myocardial oxygen consumption in the territory of the left anterior descending artery.

Summary

Background and objective: The transcerebral double-indicator dilution technique is a recently developed method to measure global cerebral blood flow at bedside. It is based on bolus injection of ice-cold indocyanine green dye and simultaneous recording of resulting thermo- and dye-dilution curves in the aorta and the jugular bulb. However, with this method 40 mL of ice-cold solution is administered as a bolus. Therefore, this prospective clinical study was performed to elucidate the effects of repeated administration of indicator on absolute blood temperature and on cerebral blood flow and metabolism.

Methods: The investigation was performed in nine male patients scheduled for elective coronary artery bypass grafting. Absolute blood temperature was measured in the jugular bulb and in the aorta before and after repeated measurements using the transcerebral double-indicator dilution technique.

Results: During the investigated time course, the blood temperature in the jugular bulb, compared to the aorta, was significantly higher with a mean difference of 0.21°C. The administration of an ice-cold bolus reduced the mean blood temperature by 0.06°C in the jugular bulb as well as in the aorta. After the transcerebral double-indicator dilution measurements a temperature recovery to baseline conditions was not observed during the investigated time period. Cerebral blood flow and cerebral metabolism did not change during the investigated time period.

Conclusions: Repeated measurements with the transcerebral double-indicator dilution technique do not affect absolute jugular bulb blood temperatures negatively. Global cerebral blood flow and metabolism measurements remain unaltered. However, accuracy and resolution of this technique is not high enough to detect the effect of minor changes of physiological variables.

Summary

Background and objective: Unanticipated difficulty in tracheal intubation in an anaesthetized patient has always been a cause of concern to anaesthesiologists. This difficulty may lead to morbidity and mortality. This survey was carried out to determine the technique commonly favoured in centres in the Oxford region in the UK for the management of unanticipated difficult intubation.

Methods: We conducted a clinical scenario-based questionnaire survey of 181 anaesthesiologists in the Oxford region. In this scenario, difficulty in endotracheal intubation is recognized only after induction of anaesthesia. A number of options were available to deal with this situation. We used this scenario as a tool to gain insight into the training and the training needs of anaesthesiologists at various levels of training.

Results: Of the 181 questionnaires sent, we received 143 (79%) completed replies. The vast majority (141/143 (99%)) of anaesthesiologists would use a gum-elastic bougie together with head and neck positioning and optimal external laryngeal manipulation to gain the best attempt at intubation. If intubation still failed, overall 129/143 (90%) had a back-up plan, while 14/143 (10%) had no plan. Flexible fibreoptic techniques were more commonly planned by 92/143 (64%) anaesthesiologists compared to blind techniques which were less commonly planned by 37/143 (26%) anaesthesiologists. Differences in choice of technique among anaesthesiologists in teaching and district general hospitals were not significant (P = 0.87). Overall, trainees were less likely to choose fibreoptic techniques compared to consultants (P = 0.0009) and would use blind techniques or ask a more experienced colleague to take over. The main reason for the choice was previous experience with the technique.

Conclusions: Although fibreoptic techniques were most commonly planned, these were less often chosen by trainees than consultants due to lack of experience/training, while unavailability of intubating laryngeal mask airway (Intavent®) was an additional issue precluding its use as an adjunct to intubation.

Summary

Background and objective: Continuous spinal anaesthesia and continuous epidural anaesthesia are both able to provide adequate postoperative pain relief. Combining local anaesthetics and opioids results in synergistic effects. The purpose of this randomized, prospective study was to compare quality of analgesia, side-effects and patient's satisfaction between spinal bupivacaine alone and epidural bupivacaine with sufentanil postoperatively.

Methods: Fifty-nine patients scheduled for hip arthroplasty were randomly assigned either to Group 1 receiving continuous spinal anaesthesia or Group 2 receiving continuous epidural anaesthesia. Postoperatively, those in Group 1 received a 1 mL bolus followed by a continuous infusion of 10 mL/24 h of bupivacaine 0.25%. Those in Group 2 received a 5 mL bolus of lidocaine 2%, followed by a continuous infusion of bupivacaine 0.25% with sufentanil 0.001 mg mL−1 at 4 mL h−1. Pain was measured using a verbal rating score and a visual analogue scale.

Results: Group 1 and Group 2 of 43.3% and 37.9% reported complete analgesia on the verbal rating score. No statistically significant difference was found in the visual analogue scale. Nausea and vomiting occurred significantly more often in Group 2. The patient satisfaction rates did not differ significantly.

Conclusions: Continuous spinal analgesia with bupivacaine alone and continuous epidural analgesia with bupivacaine/sufentanil are both effective for postoperative pain relief after hip replacement. Those patients in the epidural group reported better analgesia but had a higher rate of postoperative nausea and vomiting. Efficacy of pain therapy did not correlate with patient satisfaction.

Summary

Background and objective: To determine the optimal concentration of ropivacaine for bolus-only patient-controlled epidural labour analgesia, three different doses of ropivacaine were evaluated in comparison with bupivacaine in a double-blinded multicentre study.

Methods: Four hundred-and-fifty labouring parturients at term in three different academic institutions were randomized to four groups receiving bupivacaine 0.125% with sufentanil 0.75 μg mL−1, ropivacaine 0.125% or 0.175% with sufentanil 0.75 μg mL−1, or ropivacaine 0.2%. After an initial bolus of 10 mL of the study solution, and once visual analogue scores (VAS) were below 30 mm, patient-controlled epidural analgesia was initiated with a bolus of 4 mL, a lockout interval of 15 min and without a background infusion. Variables studied were the quality of analgesia, incidence of side-effects, the degree of motor blockade, and the mode of delivery.

Results: Bupivacaine 0.125% and ropivacaine 0.125% with sufentanil proved equally effective in providing labour analgesia without a difference in local anaesthetic consumption (48.6 ± 23 mg bupivacaine vs. 52.1 ± 38 mg ropivacaine), motor blockade or mode of delivery. Ropivacaine 0.175% plus sufentanil enhanced the quality of analgesia of the initial loading dose, whereas ropivacaine 0.2% without sufentanil increased the consumption of local anaesthetics (80.2 ± 34 mg; P < 0.05) and the degree of motor blockade.

Conclusion: Despite recent studies indicating that bupivacaine and ropivacaine may not be equipotent, both local anaesthetics provided equi-effective analgesia at equal doses without a difference in side-effects.

Summary

Background and objective: Neuromuscular block times, quality of muscle relaxation for tracheal tube insertion, and the haemodynamic effects after cisatracurium and vecuronium under sevoflurane–remifentanil anaesthesia were compared in elderly patients.

Methods: The study was performed in 40 patients over 65 yr of age. Anaesthesia was induced with thiopental, and maintained with sevoflurane in N2O/O2 and remifentanil. Cisatracurium 0.15 mg kg−1 or vecuronium 0.1 mg kg−1 were administered after induction. Intubation was attempted when neuromuscular block was 95%. Onset time, clinical duration of action, recovery index, spontaneous recovery time and tracheal intubation conditions were assessed. Haemodynamic parameters were also monitored.

Results: The average ages of the patients were 72.5 ± 5.1 and 73.6 ± 6.3 in the cisatracurium and vecuronium groups, respectively. Onset time was significantly shorter after vecuronium, 158 ± 34 s vs. 200 ± 50 s, respectively. Recovery index was significantly shorter after cisatracurium, 19.5 ± 7.5 s vs. 33.7 ± 18.6 s (P < 0.05). Clinical duration and spontaneous recovery time were similar in both groups as well as haemodynamic variables.

Conclusions: In elderly patients, vecuronium has a faster onset time while cisatracurium has a shorter recovery index under sevoflurane–remifentanil anaesthesia.

Summary

Background and objective: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration.

Methods: Eight volunteers (18–32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23–85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration–time data were analysed by compartmental and non-compartmental analysis.

Results: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00–1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00–1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean ± SD: 196 ± 65 min), total body clearance (349 ± 114 mL min−1) and volume of distribution at steady state (56 ± 14 L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fraction absorbed and half-life of the fast absorption process were 0.22 ± 0.06 and 5.2 ± 2.7 min, respectively. The values for the slow absorption process were 0.84 ± 0.14 and 386 ± 91 min, respectively.

Conclusions: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Summary

Background and objective: Eutectic mixture of local anaesthetic cream and lidocaine iontophoresis are effective in providing analgesia for peripheral venous cannulation with small gauge cannulae in adults and children. The objective of this study was to compare the analgesic efficacy of the two techniques directly in patients using larger cannulae.

Methods: In a double-blind, randomized, controlled study we compared the two techniques directly. Twenty-eight patients had the eutectic mixture of local anaesthetic cream applied to the dorsum of one hand for 60 min followed by sham iontophoresis (group EMLA); the other hand had a sham cream applied for 60 min followed by 10 min of 2 mA iontophoresis with lidocaine 4% and epinephrine 1 in 50 000 (group iontophoresis). Within 5 min of completion of iontophoresis an anaesthetist, unaware of treatment allocation, inserted 18-G venous cannulae into veins of both hands. The patient then scored the amount of pain on cannulation using a 10 point verbal rating scale.

Results: Eight patients were excluded from analysis due to failed cannulation (two group EMLA, two group iontophoresis), intolerable burning sensation from iontophoresis (one), protocol violation (one), and changes in surgical schedule (two). Pain scores were lower for the EMLA treated hand than for the iontophoresis side (median (range) 1 (0–7) vs. 3 (0–6); P = 0.023). Erythema and paraesthesia were common but short lived on the iontophoresis side.

Conclusions: Although lidocaine iontophoresis is effective more quickly than the eutectic mixture of local anaesthetic cream, the superior quality of analgesia produced by the eutectic mixture in this study should be borne in mind if these treatments are used electively.

Summary

Background and objective: We have investigated the toxic and teratogenic effects of certain non-depolarizing muscle relaxants on embryonic development in cultured rat embryos.

Methods: Rat embryos of 9.5 days were explanted and cultured in vitro for 48 h in rat serum. Whole rat serum was used as a culture medium for the control group while different concentrations of atracurium, cis-atracurium, rocuronium and mivacurium were added to rat serum for the experimental groups. Dose-dependent effects of these agents on embryonic developmental parameters were compared using morphological and biochemical methods. Each embryo was evaluated for the presence of any malformations.

Results: When compared to the control embryos, the muscle relaxants significantly decreased all growth and developmental parameters dose dependently with an increase in overall dismorphology. Among these malformations, maxillary deformity was most frequently observed. These effects were observed in much lower doses with atracurium and cis-atracurium compared to those with rocuronium and mivacurium.

Conclusions: Our results suggest that non-depolarizing muscle relaxants cause dose-dependent toxicity on rat embryos at concentrations much greater than those in clinical practice. Although, these agents seems to have a low potential for causing developmental toxicity during organogenesis, because of the lower toxic effects observed with rocuronium and mivacurium, these agents may be preferred when recurrent administrations are necessary for parturients.

Summary

Background and objective: There are concerns over the intra-cuff pressure of the laryngeal mask and laryngo-pharyngeal morbidity. In a randomized study, the authors compared cuff-pressure changes in the LMA-Classic® and the new disposable Soft Seal® laryngeal mask during nitrous oxide anaesthesia.

Methods: Two-hundred adult patients were randomly assigned to a size 4 laryngeal mask in two equal-sized groups for airway management: (a) the re-usable LMA-Classic®, or (b) the new disposable Soft Seal® laryngeal mask. Anaesthesia was administered with fentanyl, propofol, nitrous oxide, O2 and sevoflurane. The cuff pressures, adjusted to 45 mmHg at insertion, were monitored continuously until the end of the operation without any further attempt to reduce cuff pressure. On removal of the laryngeal mask, any blood at all was considered positive. Patients were requested to report any sore throat at 2 and 24 h postoperatively.

Results: During nitrous oxide anaesthesia, cuff pressures increased in the LMA-Classic® group from 45 to 100.3 mmHg and from 45 to 46.8 mmHg in the Soft Seal® laryngeal mask group (P < 0.001). The incidence of sore throat was significantly higher at 2 h postoperatively when using the LMA-Classic®, although there was no difference at 24 h following the operation. Macroscopic blood was only seen on four occasions in the LMA-Classic® group (not significant).

Conclusions: During nitrous oxide anaesthesia, cuff pressure increases in the LMA-Classic® mask were significantly higher than those of the Soft Seal® laryngeal mask. Trauma to patients, as assessed by the incidence of sore throat in the early postoperative period was significantly higher in the LMA-Classic® group. Cuff pressures should be monitored during nitrous oxide anaesthesia when LMA-Classic® is used but to do so is of less importance when using the disposable Soft Seal® laryngeal mask.

Summary

Background and objective: A retrospective analysis of applicants to Specialist Registrar training posts in anaesthesia in the Wessex Region of the UK was undertaken.

Methods: Applicants whose primary medical qualification was obtained in the European Economic Area were compared to applicants whose primary medical qualification was obtained outside it. The time since qualification, the time spent in anaesthesia, the time spent in other specialities, the post currently held and the success of the application were recorded.

Results: For doctors with a primary medical qualification from outside the European Economic Area, the median time since obtaining that qualification was 12.0 yr compared with 6.0 yr for doctors qualifying within it (P = 0.0001, U-test). Thirteen out of 89 (15%) doctors whose primary medical qualification was from outside the European Economic Area and 39 out of 61 (64%) doctors whose primary medical qualification was from within it were shortlisted for interview (P = 0.0001, χ2-test). Six out of 13 (46%) shortlisted doctors from outside the European Economic Area were appointed at interview compared with 24 out of 39 (62%) shortlisted doctors who qualified within it (P = 0.33, χ2-test).

Conclusions: In the Wessex Region of the UK, applicants whose primary medical qualification is obtained within the European Economic Area are approximately four times as likely to be shortlisted than doctors qualifying outside it. However, after shortlisting, both categories are equally likely to be successful at interview.

Summary

Background and objective: The effects of desflurane and sevoflurane on the failing myocardium are still uncertain. We investigated the effects of different concentrations of sevoflurane, desflurane and halothane in dogs with pacing induced chronic heart failure.

Methods: Global (left ventricular pressure, left ventricular dP/dt, Konigsbergtransducer) and regional myocardial function (systolic segment length shortening, ultrasonic crystals) were measured in chronically instrumented dogs with tachycardia induced severe congestive heart failure. Measurements were performed in healthy dogs and after induction of heart failure in the awake state and during anaesthesia with 0.75, 1.0, 1.25 and 1.75 minimum alveolar concentration (MAC) of halothane, sevoflurane or desflurane.

Results: The anaesthetics reduced dP/dtmax in a dose-dependent manner in healthy dogs (dP/dtmax decreased to 43–53% of awake values at 1.75 MAC). Chronic rapid left ventricular pacing increased heart rate and left ventricular end-diastolic pressure and decreased mean arterial pressure, left ventricular systolic pressure and dP/dtmax. The reduction in contractility was similar in the failing myocardium (to 41–50% of awake values at 1.75 MAC). Segmental shortening was reduced during anaesthesia by 50–62% after pacing compared with 22–44% in normal hearts. While there were similar effects of the different anaesthetics on diastolic function in healthy dogs, after induction of heart failure a more pronounced increase of the time constant of isovolumic relaxation and a greater decrease of dP/dtmin was observed with sevoflurane than with desflurane, indicating a stronger depression of diastolic function.

Conclusions: While the negative inotropic effects of sevoflurane and desflurane were similar in normal and in the failing myocardium in vivo, desflurane led to a better preservation of diastolic function in the failing myocardium.

Summary

Background and objective: Adverse effects associated with difficult airway management can be catastrophic and include death, brain injury and myocardial injury. Closed-malpractice claims have shown prolonged and persistent attempts at endotracheal intubation to be the most common situation leading to disastrous respiratory events. To date, there has been no evaluation of the types of difficult airway equipment currently available in Irish departments of emergency medicine. The objective of this survey was to identify the difficult airway equipment available in Irish departments of emergency medicine.

Methods: Departments of emergency medicine in the Republic of Ireland with at least one dedicated Emergency Medicine consultant were surveyed via telephone.

Results: All of the departments contacted held at least one alternative device on site for both ventilation and intubation. The most common alternative ventilation device was the laryngeal mask airway (89%). The most common alternative intubating device was the surgical airway device (100%).

Conclusions: Irish departments of emergency medicine compare well with those in the UK and USA, when surveyed concerning difficult airway equipment. However, we believe that this situation could be further improved by training inexperienced healthcare providers in the use of the laryngeal mask airway and intubating laryngeal mask airway, by placing greater emphasis on the ready availability of capnography and by the increased use of portable difficult airway storage units.

Summary

Background: Lidocaine has actions potentially of benefit during ischaemia–reperfusion. Neutrophils and endothelial cells have an important role in ischaemia–reperfusion injury.

Methods: Isolated human neutrophil CD11b and CD18, and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and supernatant IL-1β concentrations in response to hypoxia–reoxygenation were studied in the presence or absence of different concentrations of lidocaine (0.005, 0.05 and 0.5 mg mL−1). Adhesion molecule expression was quantified by flow cytometry and IL-1β concentrations by ELISA. Differences were assessed with analysis of variance and Student–Newman–Keuls as appropriate. Data are presented as mean ± SD.

Results: Exposure to hypoxia–reoxygenation increased neutrophil CD11b (94.33 ± 40.65 vs. 34.32 ± 6.83 mean channel fluorescence (MCF), P = 0.02), CD18 (109.84 ± 35.44 vs. 59.05 ± 6.71 MCF, P = 0.03) and endothelial ICAM-1 (146.62 ± 16.78 vs. 47.29 ± 9.85 MCF, P < 0.001) expression compared to normoxia. Neutrophil CD18 expression on exposure to hypoxia–reoxygenation was less in lidocaine (0.005 mg mL−1) treated cells compared to control (71.07 ± 10.14 vs. 109.84 ± 35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on exposure to hypoxia–reoxygenation was less in lidocaine (0.005 mg mL−1) treated cells compared to control (133.25 ± 16.05 vs. 146.62 ± 16.78 MCF, P = 0.03). Hypoxia–reoxygenation increased HUVEC supernatant IL-1β concentrations compared to normoxia (3.41 ± 0.36 vs. 2.65 ± 0.21 pg mL−1, P = 0.02). Endothelial supernatant IL-1β concentrations in lidocaine-treated HUVECs were similar to controls.

Conclusions: Lidocaine at clinically relevant concentrations decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial IL-1β concentrations.

Summary

Background and objective: To investigate the clinical application of a mathematical model of pulmonary gas exchange, which ascribes hypoxaemia to shunt and ventilation/perfusion mismatch. Ventilation/perfusion mismatch is quantified by ΔPO2, which is the drop in oxygen pressure from alveoli to lung capillaries. Shunt and ΔPO2 were used to describe changes in oxygenation after coronary artery bypass grafting.

Methods: Fourteen patients were studied 2–4 h after surgery and on postoperative days 2, 3 and 7. On each occasion inspired oxygen fraction was changed in four to six steps to obtain arterial oxygen saturation (SaO2) in the range of 90–100%, enabling construction of FeO2/SaO2 curves. Measurements of ventilation, circulation and oxygenation were entered in a previously described mathematical model of pulmonary gas exchange.

Results: We found that oxygenation was most impaired 3 days after surgery. By fitting the mathematical model to the FeO2/SaO2 curve, we found that shunt remained constant throughout the study period. However, ΔPO2 increased from 0.5 kPa (median, range 0–3.8) 2–4 h after surgery, to 3.2 kPa (range 1.2–6.4, P < 0.05) on day 2, and to 4.0 kPa (range 1.2–8.3) on day 3. On day 7, ΔPO2 decreased to 2.2 kPa (range 0–3.5, P < 0.05).

Conclusions: Ventilation/perfusion mismatch (ΔPO2), rather than shunt, explains the changes in postoperative oxygenation. The model of pulmonary gas exchange may serve as a useful and potentially non-invasive clinical tool for monitoring patients at risk of postoperative hypoxaemia.

Summary

Background and objective: Irradiation of intraoperative cell salvage blood has recently been used to inactivate tumour cells before retransfusion, during cancer surgery. No information is available about a potential inflammatory response of the recipient to the retransfusion of irradiated intraoperative cell salvage blood. This pilot study was conducted to investigate the possible release of the pro-inflammatory mediators, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), eotaxin and monocyte chemo-attractant protein-1 (MCP-1), in the serum of recipients by intraoperative retransfusion of irradiated intraoperative cell salvage blood.

Methods: Nine patients undergoing gynaecological cancer surgery were included in this study. Intraoperative cell salvage blood was irradiated with 50 Gy and retransfused to the patient. Serum and intraoperative cell salvage blood concentrations of TNF-α, IL-1β, eotaxin and MCP-1 were repeatedly analysed before and after retransfusion, respectively before and after irradiation.

Results: Traces of mediators were detected in intraoperative cell salvage blood but no increase due to irradiation was observed. Following transfusion of intraoperative cell salvage blood, minute quantities (all <30 pg mL−1) of mediators were detected in the serum of patients. However, there was no significant upregulation compared to serum values before retransfusion.

Conclusions: These results provide evidence that retransfusion of irradiated intraoperative cell salvage blood might represent a blood-saving strategy in cancer surgery without an immunological inflammatory response as shown by a lack of upregulation of inflammatory mediators.

Summary

Background and objective: We evaluated the validity of a newly developed pulse dye densitometer for indigo carmine for measuring cardiac output and circulating blood volume.

Methods: Measurements of cardiac output and circulating blood volume were performed with the indigo carmine densitometer during normovolaemia, hypovolaemia and hypervolaemia in nine mongrel dogs under general anaesthesia. The validity was evaluated by comparison of the values of cardiac output and circulating blood volume obtained by the thermodilution technique and the 51Cr-labelled red blood cell method, respectively. We also examined indigo carmine removal by continuous veno-venous haemofiltration after indigo carmine injection.

Results: There was good agreement between dye densitometer- and thermodilution-derived cardiac output (r = 0.885, P < 0.001). The bias and limits of agreement of these values were 0.09 and ± 1.07L min−1 (2 SD, n = 22), respectively. The dye-densitometer-derived circulating blood volume was greater than that of the 51Cr-labelled red blood cell method, and both values showed weak agreement (r = 0.587, P < 0.027). The sieving coefficient of indigo carmine through continuous veno-venous haemofiltration was 0.34 ± 0.06.

Conclusions: These data indicate that indigo carmine densitometry is a reliable method for cardiac output determination, but it overestimates circulating blood volume, probably due to the transition of indigo carmine into the extravascular space in the systemic circulation.

Summary

Background and objective: Acute isovolaemic haemodilution increases local and mean cerebral blood flow. It is not known whether a single haemodilution has a short-term effect only or whether it affects cerebral perfusion over a longer time period. In the present study, local and mean cerebral blood flow were determined in conscious rats after a 4, 24 and 48 h period following one-time haemodilution.

Methods: Thirty-six rats were randomized to three untreated sham groups and three groups of haemodilution (4, 24 or 48 h, n = 6 for each group). Isovolaemic haemodilution with albumin 5% aimed to a target haematocrit of 0.2. Local cerebral blood flow was measured in 38 brain regions by the iodo-[14C]antipyrine method in conscious normothermic rats.

Results: Isovolaemic haemodilution reduced haematocrit from 0.44 to 0.20. During the following 24 and 48 h periods, haematocrit remained low (0.22 and 0.21). Mean cerebral blood flow was similar in untreated sham groups (88 ± 12 after 4 h, 92 ± 11 after 24 h, 96 ± 10 mL 100 g−1 min−1 after 48 h). Haemodilution increased mean cerebral blood flow after 4 h (184 ± 11 mL 100 g−1 min−1), after 24 h (153 ± 13 mL 100 g−1 min−1) and 48 h (149 ± 15 mL 100 g−1 min−1) (P ≤ 0.05). Local cerebral blood flow increased in all 38 structures after 4 h haemodilution but decreased with time in six of 38 brain structures after 24 h and in 15 regions after 48 h (P ≤ 0.05).

Conclusions: A single one-time haemodilution increased mean cerebral blood flow for 2 days. However, local adaptation of cerebral blood flow to a chronic low haematocrit occurred but was heterogeneous within the brain.

Summary

Background and objective: The time course of action of mivacurium does not correlate with its rapid breakdown by plasma cholinesterase. Pharmacokinetic–pharmacodynamic (PK–PD) modelling was applied to obtain more insight in the concentration–effect relationship.

Methods: Fourteen patients between 25 and 55 yr, undergoing non-major surgery, American Society of Anesthesiologists Grade I–II, were included. All patients received thiopentone/fentanyl/isoflurane/oxygen/nitrous oxide anaesthesia. Neuromuscular block was monitored mechanomyographically using single twitch stimulation (0.1 Hz). Mivacurium was administered as a short-term infusion, mean (standard deviation) duration 4.7 (1.0) min and dose 145 (33) μg kg−1. Arterial blood samples were obtained, and plasma was analysed using high performance liquid chromatography. PK–PD modelling was performed using an iterative Bayesian two-stage approach, assuming that the trans–trans and cis–trans isomers are equally potent.

Results: A PK–PD model with an effect compartment linked to plasma did not fit to the data satisfactorily. A model using an interstitial space compartment between plasma and effect compartment fitted significantly better. Parameters (mean (percentage coefficient of variation)) of the best fitting model were: kip 0.374 min−1 (46%), kei 0.151 min−1 (36%), EC50 98 μg L−1 (29%) and γ 3.7 (22%).

Conclusions: The PK–PD behaviour of mivacurium could be described using a model with an interstitial space compartment interposed between plasma and effect compartment. This model shows that the time course of mivacurium is mainly governed by the concentration decline in this interposed compartment and only indirectly related to the rapid plasma clearance.