BMC Anesthesiology - Latest Articles

Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation.

James Jarman — 2009-06-10T00:00:00Z

Background: Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings. Methods: Quadruplicate ex vivo human chorionic plate arterial rings were used in all studies. Series 1 and 2 examined the role of the K+ channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K+ (KCa++) channels (Series 1A+B) or glibenclamide, which blocks the ATP sensitive K+ (KATP) channel (Series 2), modulated sevoflurane-mediated vasodilation. Series 3 – 5 examined the role of the Ca++ channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca++ channel (Series 3), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca++ channels (Series 4A+B), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca++ channel (Series 5A+B), modulated sevoflurane-mediated vasodilation. Results: Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the KCa++ and KATP channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K+ channels. Blockade of the voltage-operated Ca++channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca++channels did not alter sevoflurane vasodilation. Conclusion: Sevoflurane appears to block chorionic arterial KCa++ and KATP channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the in vitro foeto-placental circulation.

Head CT is of limited diagnostic value in critically ill patients who remain unresponsive after discontinuation of sedation

Jay Balachandran — 2009-05-07T00:00:00Z

Background: Prolonged sedation is common in mechanically ventilated patients and is associated with increased morbidity and mortality. We sought to determine the diagnostic value of head computed tomography (CT) in mechanically ventilated patients who remain unresponsive after discontinuation of sedation. Methods: A retrospective review of adult (age >18 years of age) patients consecutively admitted to the medical intensive care unit of a tertiary care medical center. Patients requiring mechanical ventilation for management of respiratory failure for longer than 72 hours were included in the study group. A group that did not have difficulty with awakening was included as a control. Results: The median time after sedation was discontinued until a head CT was performed was 2 days (interquartile range 1.375–2 days). Majority (80%) of patients underwent head CT evaluation within the first 48 hours after discontinuation of sedation. Head CT was non-diagnostic in all but one patient who had a small subarachnoid hemorrhage. Twenty-five patients (60%) had a normal head CT. Head CT findings did not alter the management of any of the patients. The control group was similar to the experimental group with respect to demographics, etiology of respiratory failure and type of sedation used. However, while 37% of subjects in the control group had daily interruption of sedation, only 19% in the patient group had daily interruption of sedation (p < 0.05). Conclusion: In patients on mechanical ventilation for at least 72 hours and who remain unresponsive after sedative discontinuation and with a non-focal neurologic examination, head CT is performed early and is of very limited diagnostic utility. Routine use of daily interruption of sedation is used in a minority of patients outside of a clinical trial setting though it may decrease the frequency of unresponsiveness from prolonged sedation and the need for head CT in patients mechanically ventilated for a prolonged period.

Efficacy of Sub-Tenon's block using an equal volume of local anaesthetic administered either as a single or as divided doses.a randomised clinical trial

Ehtesham Khan — 2009-03-26T00:00:00Z

Background: Sub-Tenon's anaesthetic is effective and reliable in producing both akinesia and anaesthesia for cataract surgery. Our clinical experience indicates that it is sometimes necessary when absolute akinesia is required during surgery to augment the block with 1–2 ml of local anaesthetic. Hypothesis was that after first injection some of the volume injected may spill out and before second injection the effect of hyaluronidase has taken place and second volume injectate will have desired effect. Methods: A prospective, randomised, control trial in which patients were randomly allocated to one of two groups. In group 1, single injection of 5 ml of local anaesthetic was injected. In group 2, 3 ml of the same anaesthetic solution was injected followed by application of gentle orbital pressure for 2 minutes. A further 2 ml of the same anaesthetic solution was injected through the same conjunctival incision. Measurement of movement in four quadrants of eye was done by the surgeon at 3 and 6 minutes. Intraocular pressure, chemosis, and subconjuctival haemorrhage were also measured. Results: Significant differences at 3 minutes between groups for overall movement, medial, superior, and lateral quadrants occurred. At 6 minutes no significant group differences emerged for the overall movement or for any of four quadrants. Conclusion: Single injection of local anaesthesia for sub-Tenon's block with mixture of lignocaine with adrenaline, bupivacaine and hyaluronidase was found to be superior to provide akinesia of ocular muscles compared to divided dose given by two injections. No difference in groups in terms of haemorrhage, chemosis, patient's satisfaction and intraocular pressure was found.Trial registrationTrial registration no-ISRCTN73431052

Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial

Edith Fleishmann — 2009-02-03T00:00:00Z

Background: Even the best cancer surgery is usually associated with minimal residual disease. Whether these remaining malignant cells develop into clinical recurrence is at least partially determined by adequacy of host defense, especially natural killer cell function. Anesthetics impair immune defenses to varying degrees, but nitrous oxide appears to be especially problematic. We therefore tested the hypothesis that colorectal-cancer recurrence risk is augmented by nitrous oxide administration during colorectal surgery. Methods: We conducted a 4- to 8-year follow-up of 204 patients with colorectal cancer who were randomly assigned to 65% nitrous oxide (n = 97) or nitrogen (n = 107), balanced with isoflurane and remifentanil. The primary outcome was the time to cancer recurrence. Our primary analysis was a multivariable Cox-proportional-hazards regression model that included relevant baseline variables. In addition to treatment group, the model considered patient age, tumor grade, dissemination, adjacent organ invasion, vessel invasion, and the number of nodes involved. The study had 80% power to detect a 56% or greater reduction in recurrence rates (i.e., hazard ratio of 0.44 or less) at the 0.05 significance level. Results: After adjusting for significant baseline covariables, risk of recurrence did not differ significantly for nitrous oxide and nitrogen, with a hazard ratio estimate (95% CI) of 1.10 (0.66, 1.83), P = 0.72. No two-way interactions with the treatment were statistically significant. Conclusion: Colorectal-cancer recurrence risks were not greatly different in patients who were randomly assigned to 65% nitrous oxide or nitrogen during surgery. Our results may not support avoiding nitrous oxide use to prevent recurrence of colorectal cancer.Implications StatementThe risk of colorectal cancer recurrence was similar in patients who were randomly assigned to 65% nitrous oxide or nitrogen during colorectal surgery.Trial RegistrationCurrent Controlled Clinical Trials NCT00781352 http://www.clinicaltrials.gov

Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

Katherine Roberts — 2008-12-17T00:00:00Z

Background: The Contact Heat Evoked Potential Stimulator (CHEPS) utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Aδ and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli. Methods: In this study we have recorded evoked potentials stimulated by 51°C contact heat pulses from CHEPS using EEG, under normal conditions (baseline), and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS). Results: Analysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD) changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG) and the psychophysical perception of pain on the VAS. Conclusion: The results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain activity indicative of pain and pro-nociceptive sensitisation in healthy subjects and chronic pain patients. Further studies are required for the technique to progress as a useful tool in clinical trials of novel analgesics.

Arteriovenous extracorporeal lung assist allows for maximization of oscillatory frequencies: a large-animal model of respiratory distress

Ralf Muellenbach — 2008-11-14T00:00:00Z

Background: Although the minimization of the applied tidal volume (VT) during high-frequency oscillatory ventilation (HFOV) reduces the risk of alveolar shear stress, it can also result in insufficient CO2-elimination with severe respiratory acidosis. We hypothesized that in a model of acute respiratory distress (ARDS) the application of high oscillatory frequencies requires the combination of HFOV with arteriovenous extracorporeal lung assist (av-ECLA) in order to maintain or reestablish normocapnia. Methods: After induction of ARDS in eight female pigs (56.5 ± 4.4 kg), a recruitment manoeuvre was performed and intratracheal mean airway pressure (mPaw) was adjusted 3 cmH2O above the lower inflection point (Plow) of the pressure-volume curve. All animals were ventilated with oscillatory frequencies ranging from 3–15 Hz. The pressure amplitude was fixed at 60 cmH2O. At each frequency gas exchange and hemodynamic measurements were obtained with a clamped and de-clamped av-ECLA. Whenever the av-ECLA was de-clamped, the oxygen sweep gas flow through the membrane lung was adjusted aiming at normocapnia. Results: Lung recruitment and adjustment of the mPaw above Plow resulted in a significant improvement of oxygenation (p < 0.05). Compared to lung injury, oxygenation remained significantly improved with rising frequencies (p < 0.05). Normocapnia during HFOV was only maintained with the addition of av-ECLA during frequencies of 9 Hz and above. Conclusion: In this animal model of ARDS, maximization of oscillatory frequencies with subsequent minimization of VT leads to hypercapnia that can only be reversed by adding av-ECLA. When combined with a recruitment strategy, these high frequencies do not impair oxygenation

Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

Gregory Hammer — 2008-10-06T00:00:00Z

Background: Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children. Methods: Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints. Results: Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined. Conclusion: Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.

Determination of the efficacy and side-effect profile of lower doses of intrathecal morphine in patients undergoing total knee arthroplasty.

Patrick Hassett — 2008-09-24T00:00:00Z

Background: Intrathecal (IT) morphine provides excellent post-operative analgesia, but causes multiple side effects including nausea and vomiting (PONV), pruritus and respiratory depression, particularly at higher doses. The lowest effective dose of spinal morphine in patients undergoing total knee arthroplasty is not known. Methods: We evaluated the analgesic efficacy and side effect profile of 100 – 300 μg IT morphine in patients undergoing elective total knee replacement in this prospective, randomized, controlled, double-blind study. Sixty patients over the age of 60 undergoing elective knee arthroplasty were enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg Bupivacaine and IT morphine in three groups: (i) 100 μg; (ii) 200 μg; and (iii) 300 μg. Results: Both 200 μg and 300 μg IT morphine provided comparable levels of postoperative analgesia. However, patients that received 100 μg had greater pain postoperatively, with higher pain scores and a greater requirement for supplemental morphine. There were no differences between groups with regard to PONV, pruritus, sedation, respiratory depression or urinary retention. Conclusion: Both 200 μg and 300 μg provided comparable postoperative analgesia, which was superior to that provided by 100 μg IT morphine in patients undergoing total knee arthroplasty. Based on these findings, we recommend that 200 μg IT morphine be used in these patients.Trial registrationClinicalTrials.gov Identifier NCT00695045

Desflurane consumption during automated closed-circuit delivery is higher than when a conventional anesthesia machine is used with a simple vaporizer-O2-N2O fresh gas flow sequence.

Sofie De Cooman — 2008-07-17T00:00:00Z

Background: The Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction. Methods: Thirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively) was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10), the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA. Results: Age and weight did not differ between the groups (P > 0.05), but patients in the Zeus group were taller (P = 0.04). In the Zeus group, the desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was higher in the Zeus group at all times, a difference that persisted after correcting for the small difference in FA between the two groups. Conclusion: Agent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s) that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.

A prospective study to evaluate the accuracy of pulse power analysis to monitor cardiac output in critically ill patients

Maurizio Cecconi — 2008-02-18T00:00:00Z

Background: Intermittent measurement of cardiac output may be performed using a lithium dilution technique (LiDCO). This can then be used to calibrate a pulse power algorithm of the arterial waveform which provides a continuous estimate of this variable. The purpose of this study was to examine the duration of accuracy of the pulse power algorithm in critically ill patients with respect to time when compared to measurements of cardiac output by an independent technique. Methods: Pulse power analysis was performed on critically ill patients using a proprietary commercial monitor (PulseCO). All measurements were made using an in-dwelling radial artery line and according to manufacturers instructions. Intermittent measurements of cardiac output were made with LiDCO in order to validate the pulse power measurements. These were made at baseline and then following 1, 2, 4 and 8 hours. The LiDCO measurement was considered the reference for comparison in this study. The two methods of measuring cardiac output were then compared by linear regression and a Bland Altman analysis. An error rate for the limits of agreement (LOA) between the two techniques of less than 30% was defined as being acceptable for this study. Results: 14 critically ill medical and surgical patients were enrolled over a three month period. At baseline patients showed a wide range of cardiac output (median 7.5 L/min, IQR 5.1 -9.0 L/min). The bias and limits of agreement between the two techniques was deemed acceptable for the first four hours of the study with percentage errors being 29%, 22%, and 285 respectively. The percentage error at eight hours following calibration increased to 36%. The ability of the PulseCo to detect changes in cardiac output was assessed with a similar analysis. The PulseCO tracked the changes in cardiac output with adequate accuracy for the first four hours with percentage errors being 20%, 24% and 25%. However at eight hours the error had increased to 43%. Conclusion: The agreement between lithium dilution cardiac output and the pulse power algorithm in the PulseCO monitor remains acceptable for up to four hours in critically ill patients.