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Correspondence European Journal of Anaesthesiology 2012, 29:246–254
ECG changes during in-situ hypothermic liver resections Francois M. Carrier, Claudia Tanase, Salima Naili, Tonine Bartelmaos, Daniel Azoulay and Dan Benhamou From the Centre Hospitalier de l’Universite´ de Montre´al, Montreal, Quebec, Canada (FMC), Department of Anaesthesiology (FMC, CT, SN, TB, DB) and Department of Hepato-Biliary Surgery, Hoˆpital Paul-Brousse (DA), Villejuif, France Correspondence to Francois M. Carrier, MD, Department of Anaesthesiology, Hopital Paul-Brousse, 12–14 Avenue Paul-Vaillant-Couturier, 94804 Villejuif, France Tel: +33 1 4559 3219; fax: +33 1 4559 3834; e-mail: [email protected] Published online 28 October 2011
Editor, Liver resection is increasingly performed to remove colorectal metastases.1 It provides clinical benefits through complete resection of the neoplastic material.2 Surgical techniques are improving to extend this therapy to more patients and complex situations.3 When major resection with vascular reconstruction is deemed necessary, in-situ hypothermic liver resection becomes an option. It is thought to better preserve liver function when a long ischemic time is needed for parenchyma resection and vascular reconstruction.4 To decrease liver temperature, a topical cooling technique can be used alone or with portal hypothermic perfusion. Such techniques have major implications for the anaesthesiologist, such as potential hemodynamic instability, coagulopathy, hypothermia and hyperkalaemia.5 This article describes the occurrence of ECG changes that were observed during two major liver resections while using a topical cooling technique. When we started using hypothermic liver resection in our centre, liver hypothermia was achieved with topical cooling only. During two of these cases, unexpected ECG changes were observed. The first patient, a 43-year-old man without specific past medical history, was scheduled for open right hepatectomy. After dissection, topical cooling of the liver was induced by placing wet icy cold gauzes both in the retro-hepatic space and over the superior border of the liver. When the surgeon mobilised the liver to start the resection, cold gauzes inserted over the superior border of the liver came into contact with the diaphragm. The patient then developed ST segment depression and profound T wave inversion on DII and V5 derivations. These changes rapidly disappeared when the gauzes were removed, but reappeared quickly after the gauzes were reinserted. Figure 1a shows the preoperative ECG. Figure 1b shows ECG changes 2 min following gauze placement. Figure 1c shows the ECG
immediately after removal of the gauzes. A couple of minutes later, the same changes were observed when the gauzes were reinserted in the same space (Fig. 1d). The gauzes placed over the superior border of the liver were then completely removed. A couple of months later, the same changes were observed in a 51-year-old man just after the gauzes over the superior border of the liver had been placed. On the basis of our previous experience, the gauzes were rapidly removed and the ECG normalised (not shown). As the ECG changes were rapidly detected, the contact time between the gauzes and the diaphragm lasted only few minutes. In neither of these patients arrhythmias or hemodynamic instability were noted. Changes (if any) of cardiac function could not be demonstrated, as a transesophageal echocardiography probe was not inserted and not available at the time of the events. The use of cold gauzes over the superior border of the liver during in-situ hypothermic liver resection with topical cooling seems to induce ECG changes. As the liver is very close to the right ventricle, a local effect on epicardial repolarisation might explain the observed changes.6 This technique could have also induced a return of cold blood to the right ventricle, similar to that observed during orthotopic liver transplantation. However, significant temperature changes deep inside the liver might well take a few minutes under topical cooling. ECG changes were observed seconds after placement of gauzes and started to recede very soon after their removal, suggesting a local effect. Indeed, similar but more sustained ECG changes due to possible hypothermic–osmotic damages have been reported in paediatric cardiac patients after topical cooling of the heart with ice.7 In our patients, both the short contact time and the relative protection of the heart offered by the diaphragm likely prevented sustained changes such as arrhythmia or hemodynamic instability. To our knowledge, this is the first report of ECG changes due to local cardiac cooling during non-cardiac surgery. After these observations were made, the cooling technique was modified and cold gauzes placed above the liver are now separated from the diaphragm by gauzes at ambient temperature. Moreover, we now use an intrahepatic cooling technique with portal hypothermic perfusion of the liver that depends less on the use of cold gauzes. When performing this technique, a porto-venovenous bypass is first inserted and then both the retrohepatic space and the superior border of the liver are packed with icy cold gauzes as described above. Total liver vascular exclusion is performed and cold graft preservation solution is infused through the portal vein and
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Fig. 1
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Azarov JE, Shmakov DN, Vityazev VA, et al. Ventricular repolarization pattern under heart cooling in the rabbit. Acta Physiol 2008; 193:129–138. Corno A, Zoia E, Santoro F, et al. Epicardial damage induced by topical cooling during paediatric cardiac surgery. Br Heart J 1992; 67:174–176. DOI:10.1097/EJA.0b013e32834d86d8
Bilateral bispectral index differences in asymptomatic internal carotid stenosis (a) Basal ECG. (b) ECG after placement of cold gauzes. (c) ECG immediately after removal of gauzes. (d) ECG after the gauzes were reinserted in the same space.
Marı´a J. Estruch-Pe´rez, Juan Soliveres-Ripoll, Josep BalaguerDomenech, Lorena Go´mez-Diago, Alicia Sanchez-Hernandez and Cristina Solaz-Rolda´n From the Anaesthesiology and Critical Care Department, Dr Peset University Hospital, Valencia, Spain (MJEP, JSR, JBD, LGD, ASH, CSR)
drained from a retro-hepatic cavotomy. When surgery is completed, the preservation solution is flushed and the bypass weaned. In our experience, this technique is associated with a lower systemic temperature and a more sudden return of cold blood after unclamping. Nevertheless, no profound ECG changes such as those described previously have been observed with the modified technique which is consistent with a local effect hypothesis. Moreover, portal hypothermic perfusion is not only associated with an intra-hepatic cooling effect which depends less on topical gauzes, but it is the only technique that has been associated with improved clinical outcome.4,5 We suggest that during in-situ hypothermic liver resection, cold gauzes over the superior border of the liver should be separated from the diaphragm to avoid the occurrence of ECG changes. Moreover, a portal hypothermic perfusion technique might be preferred.
Acknowledgements The authors would like to thank Dr Marie-Christine Gillon for her assistance in data retrieval and Miss Nadia Morfousse for her clerical work. The Royal College of Physicians and Surgeons of Canada supported this work by a fellowship grant. None of the authors has any conflict of interest.
References 1
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3 4
5
Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009; 27:3677–3683. Wei AC, Greig PD, Grant D, et al. Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol 2006; 13:668–676. Berri RN, Abdalla EK. Curable metastatic colorectal cancer: recommended paradigms. Curr Oncol Rep 2009; 11:200–208. Azoulay D, Eshkenazy R, Andreani P, et al. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg 2005; 241:277–285. DuBay D, Gallinger S, Hawryluck L, et al. In situ hypothermic liver preservation during radical liver resection with major vascular reconstruction. Br J Surg 2009; 96:1429–1436.
Correspondence to Marı´a J. Estruch Pe´rez, MD, Anesthesiology and Critical Care Department, Dr Peset University Hospital, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain E-mail: [email protected] Published online 10 January 2012
Editor, An unexpected bispectral index (BIS) decrease may indicate inadequate cerebral perfusion.1 Further, BIS may be useful for monitoring carotid artery disease.2,3 Differences in BIS values from two electrodes applied simultaneously to the same patient have been reported.4 We describe a patient who, while under simultaneous bilateral BIS monitoring, suffered a right-side fall in BIS values. A hypertensive, 72-year-old male patient underwent bilateral inguinal hernia repair under local anaesthesia and deep sedation. We obtained the patient’s explicit consent to publish his data in this case report. After standard monitoring, continuous three-lead ECG, continuous SpO2 and 5 min interval blood pressure determinations were recorded. Two BIS quattro sensors (Covidien, Medical, Boulder, CO, USA) were applied to each side of the forehead (right and left) and connected to two BIS Vista monitors (Covidien) as part of a clinical trial. Clocks on the two monitors were synchronised just before monitoring the patient. Bilateral BIS readings were recorded every minute. A unique bolus of 0.1 mg fentanyl and 160 mg propofol was intravenously administered, followed by a 6 mg kg1 h1 continuous propofol infusion. No additional medication was given. A laryngeal mask was placed and 50% oxygen in air spontaneous breathing was allowed. Field block was performed using 20 ml 1% mepivacaine. After 10 min, the suppression ratio began to increase progressively, especially on the right side. No mean blood pressure change was observed. After 20 min, BIS values from the right electrode suddenly decreased and the European Journal of Anaesthesiology
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Minute Changes in values of bispectral index (BIS), in suppression ratio (SR) and non invasive blood pressure values (NIBP) during the whole surgery. NIBP determinations (mmHg) can be read from each vertical bar. SBP (top of the bar), mean blood pressure (middle) and DBP (bottom) are shown. L-BIS, left-side BIS; R-BIS, right-side BIS; L-SR, left BIS suppression ratio; R-SR, right BIS suppression ratio.
suppression ratio of the right electrode increased simultaneously (Fig. 1). A manually started blood pressure determination showed hypotensive blood pressure values; thus, propofol infusion was stopped and 100% oxygen was administered and blood pressure was increased using volume expanders. There were no concomitant changes in the other standard monitoring values. Eight minutes later, blood pressure had returned to previous values despite the right-side BIS value remaining lower than the left one for almost 20 min. A correlation between blood pressure and BIS difference could be observed.
Fig. 2
By the time the patient emerged from deep sedation, the two BIS values were not significantly different. Postoperative course was uneventful. No intraoperative awareness was found. As the neurological examination was normal (done by the anaesthesiologist), unilateral transient ischaemia was suspected. No further cerebral image diagnostic tests were made. As carotid echo Doppler test is highly available, it showed a right carotid stenosis. The arteriography revealed over 70% right stenosis (Fig. 2). The patient was scheduled for right carotid stent placement. The asymmetric BIS values alerted us to a possible vascular incident with concomitant cerebral ischaemia leading to permanent low BIS values of the right-sided electrode.
Arteriography of the carotid stenosis.
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Correspondence 249
BIS value changes can be observed during periods at risk of cerebral hypoperfusion, such as the carotid crossclamping period.2,3 These findings need further studies to be conclusive. A 70-year-old patient with bilateral internal carotid artery stenosis was reported to have shown a sudden BIS value asymmetry after temporary bypass during a left carotid endarterectomy, as a sign of reperfusion. In the second operation for the right side, no marked discrepancy between the two sides was observed.5 In cases of internal carotid stenosis, discrepancies in BIS and state entropy values have also been seen during general surgery.6,7 The decrease in the BIS signal observed in our patient could indicate a low right frontal cortical activity, assumably due to cerebral hypoperfusion caused by a considerable decrease in blood pressure. However, blood pressure returned to previous levels, whereas the BIS asymmetry remained until the end of surgery. The large and unexpected decrease in BIS values made us think about an ischaemic event or inadequate cerebral perfusion as a result of a carotid stenosis, as it has been reported previously during carotid surgery.5–7 Although small discrepancies in BIS values from sensors placed on each side of the forehead are recognised as normal, a unilateral decrease in BIS values should be considered important and investigated, especially in patients with cardiovascular risk factors, as it can be an indicator of asymptomatic internal carotid stenosis. The timely diagnosis of cerebral hypoperfusion during general anaesthesia is not only limited to an EEG specialist, but may be achieved by the attendant anaesthesiologist as well.
Acknowledgement There are no financial supports or sponsorships or conflicts of interest or assistance with the study to declare.
References 1
2
3
4 5
6
7
Morimoto Y, Monden Y, Ohtake K, et al. The detection of cerebral hypoperfusion with bispectral index monitoring during general anesthesia. Anesth Analg 2005; 100:158–161. Estruch-Pe´rez MJ, Barbera´-Alacreu M, Ausina-Aguilar A, et al. Bispectral index variations in patients with neurological deficits during awake carotid endarterectomy. Eur J Anaesthesiol 2010; 27:359–363. Bonhomme V, Quentin D, Thierry L, et al. Bispectral index profile during carotid cross clamping. J Neurosurg Anesthesiol 2007; 19:49–55. Niedhart DJ, Kaiser HA, Jacobsohn E, et al. Intrapatient reproducibility of the BISxp monitor. Anesthesiology 2006; 104:242–248. Kodaka M, Nishikawa Y, Suzuki T, et al. Does bilateral bispectral index monitoring (BIS) detect the discrepancy of cerebral reperfusion during carotid endarterectomy? J Clin Anesth 2009; 21:431–434. Lee EH, Choi IC, Song JG, et al. Different bispectral index values from both sides of the forehead in unilateral carotid artery stenosis. Acta Anaesthesiol Scand 2009; 53:134–136. Khan QS, Ozcan MS. Disagreement in bilateral state entropy values in carotid artery disease. J Neurosurg Anesthesiol 2011; 23:51–52. DOI:10.1097/EJA.0b013e32834f5f26
Datex-Ohmeda NeuroMuscular Transmission electromyography module artefacts in clinical practice: case report and retrospective chart review Philippe E. Dubois, John Mitchell, Christophe Dransart and Alain d’Hollander From the Department of Anaesthesiology, University of Louvain, CHU MontGodinne, Yvoir, Belgium (PED, JM, CD) and Department of Anaesthesiology, University Hospital, Geneva, Switzerland (Ad’H) Correspondence to Dr Philippe E. Dubois, Department of Anaesthesiology, CHU Mont-Godinne, 1 Avenue Therasse, B-5530 Yvoir, Belgium Tel: +32 81423929; fax: +32 81423920; e-mail: [email protected] Published online 1 March 2012
Editor, Inducing a neuromuscular block (NMB) has advantages for the anaesthetist and the surgeon, but exposes the patient to the risk of residual curarisation.1 This can be reduced using various methods of quantitative NMB monitoring.2 The NeuroMuscular Transmission Module (M-NMT) (GE Healthcare, Hatfield, UK; formerly Datex-Ohmeda, Helsinki, Finland) uses kinemyography or electromyography (EMG). The module can record and display data throughout the period of NMB and save the data in the anaesthesia record (AS/5 monitor Gangwon-do, Korea). EMG measures muscle electrical activity using surface electrodes that can be easily attached to the hand, among other sites. The EMG responses are acknowledged to be consistent over time and less sensitive to changes in the position of the hand than acceleromyography3 and, probably, less than kinemyography.4 Given these advantages, continuous quantitative monitoring of NMB by EMG has gradually been adopted in clinical practice in our institution. Unfortunately, numerous recordings provided illogical trends of the NMB. To illustrate the aberrant results provided by the device in some clinical cases, we report data obtained from a 95-kg patient who underwent abdominal surgery under general anaesthesia (Fig. 1). EMG monitoring was started in operating room according to the Datex-Ohmeda Neuromuscular monitoring guide5 and in accordance with good clinical practice.6 The stimulating electrodes (E152, IMMED, Bio Protech Inc., Gangwon-do, Korea) were applied to the wrist over the ulnar nerve. The recording electrode was placed on the thenar eminence over the belly of the adductor pollicis muscle and the indifferent electrode was placed on the first phalanx of the thumb. The neutral ground electrode was placed over the carpal ligament on the inner surface of the wrist. The automatic calibration sequence was completed before administering rocuronium by searching for the supramaximal stimulation level and 100% calibration of twitch height (T1). This was followed by 2-Hz train-of-four (TOF) stimulations every 20 s, with the EMG responses (TOF count, T1 and TOF ratio) recorded online. European Journal of Anaesthesiology
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Fig. 1 roc 50 mg
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The Datex-Ohmeda NeuroMuscular Transmission Module (M-NMT) windows during a neuromuscular block monitored by electromyography (EMG) as displayed on the AS/5 anaesthesia monitor. (a) The trends window is shown. The first twitch height (T1) is represented as a percentage of the initial calibration by dots; the train-of-four (TOF) count is represented by crosses and the TOF ratio (T4/T1) is represented as a percentage by vertical lines. The thick black line indicates the time of recording of the data (b and c). (b) The four EMG responses with reference to the EMG from the initial calibration (in grey) are shown. (c) The numeric values for TOF ratio, TOF count and T1 are shown.
Shortly after administering rocuronium 50 mg, four small responses reappeared on the screen in response to the TOF stimulations. The calculated TOF ratio was more than 0.9. Surprisingly, this figure fell gradually as the T1 height increased. The EMG responses did not disappear after further boluses of rocuronium 10 mg, and the TOF ratio remained high until surgery ended. Sugammadex 200 mg enabled rapid recovery of four responses with T1 more than 100% and without fade (TOF ratio > 0.9) and made it possible to extubate the patient in the absence of residual block. The main problem was the unexpected recording of the four small responses that persisted during deep and moderate blockade (Fig. 1b). Only two actual muscular EMG responses were recorded within the four identical artefacts. However, the device interpreted them as four real twitches (T1: 12% and TOF count: 4; Fig. 1c). The TOF ratio was inappropriately calculated (83%, GE Healthcare) and increased after further administration of rocuronium. To determine how frequently this problem arises in our clinical practice, we carried out a chart review to objectively assess the quality of the EMG recordings provided by the Datex-Ohmeda M-NMT module. Following Institutional Ethics Committee approval (CHU MontGodinne om 050, 69/2011), 100 EMG recordings of nondepolarising NMB randomly selected over a period of 1 year were analysed retrospectively. The patients’ mean (SD) age was 51 (19) years and BMI was 26 (5) kg m2 and they underwent various types of surgery. Rocuronium 0.48 (0.11), atracurium 0.45 (0.10) and cisatracurium 0.13 (0.05) mg kg were administered to 68, 30 and two patients, respectively. Neostigmine was administered in 45% of cases.
The initial EMG was properly calibrated in 72 cases. Taking into account whether or not the initial calibration was carried out, the quality of various aspects of the EMG recordings was assessed: the capacity to determine the TOF count gradually (from 1 to 4) – 82 and 54% of cases, respectively; whether the early trend of TOF ratio was considered consistent (gradually increasing from an initial level <50%, and inter-measurement variability <15%) – 34 and 25% of cases, respectively; and, conversely, if the TOF ratio’s final assessment was consistent – in 91 and 71% of cases, respectively. We have shown that when using the M-NMT DatexOhmeda module, problems may exist regarding the interpretation of the EMG recordings to the point where this limited their usefulness in managing the NMB. In particular, the detection of four small, almost identical EMG responses shortly after the induction of the block resulted in an incorrect calculation of a TOF count and a high TOF ratio. This problem frequently led to the false assumption that the patient was not completely paralysed (up to 75% of cases in the absence initial calibration). The presence of these small responses without fade during deep block was previously attributed to direct muscular stimulation. However, recent studies have shown that the current used in NMB monitoring (pulse duration 0.2 ms, intensity 10–60 mA) was usually inadequate to induce genuine muscular stimulations.7 Thus, other reasons specific to the method of EMG recording used by the Datex-Ohmeda M-NMT module probably contributed to the artefactual detection of these small responses. Further prospective investigation should be undertaken to determine the cause. During NMB recovery, as ‘real’ twitches appear and then increase, they replace the artefacts and the calculated TOF ratio decreases progressively (as the real twitches exhibit fade), before increasing again until as fade disappears towards the end of recovery (Fig. 1a). The quality of the TOF ratio measurements increased with the intensity of the muscular responses recorded, reducing the impact of artefacts at the end of the case. However, in 29% of cases when initial calibration had not been performed, it was not possible to rule out residual curarisation before the patient awoke. We have shown that the recordings were of a better quality when calibration was undertaken prior to administering rocuronium. Even if artefacts remain, it seems useful to calibrate the initial twitches to limit the magnitude of electrical interference during the recording of the muscular responses. In conclusion, artefacts alter EMG recordings provided by the Datex-Ohmeda M-NMT module, particularly during deep and moderate block. Additional technical improvements are needed to guarantee clinicians correct management of NMB in all patients.
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Correspondence 251
Acknowledgements This work was supported by departmental funds. A.d’.H. is a non-remunerated consultant and board member of Medical Devices Bio Engineering-sprl, Waterloo, Belgium.
References 1
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Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part 1. Definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg 2010; 111:120–128. Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II. Methods to reduce the risk of residual weakness. Anesth Analg 2010; 111:129–140. Ha¨nzi P, Leibundgur D, Wessendorf R, et al. Clinical validation of electromyography and acceleromyography as sensors for muscle relaxation. Eur J Anaesthesiol 2007; 24:882–888. Dahaba AA, Von Klobucar F, Rehak PH, List WF. The neuromuscular transmission module versus the relaxometer mechanomyograph for neuromuscular block monitoring. Anesth Analg 2002; 94:591–596. Brull SJ, Paloheimo M. A practical guide to monitoring neuromuscular function. Datex-Ohmeda Division Instrumentarium Corp. Helsinki, Finland; 2002. Fuchs-Buder T, Claudius C, Skovgaard LT, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007; 51:789–808. Kopman AF. Can conventional peripheral nerve stimulators induce direct muscle depolarization? Anesth Analg 2006; 102:1905. DOI:10.1097/EJA.0b013e32834f8f76
The efficacy of continuous infusion of low dose dexmedetomidine for postoperative patients recovering in general wards Hiroko Iwakiri, Yutaka Oda, Akira Asada and Makoto Ozaki From the Department of Anesthesiology, Tokyo Women’s Medical University 8–1 Kawadacho, Shinjuku-ku, Tokyo, (HI, MO) and Department of Anesthesiology, Osaka City University Graduate School of Medicine 1–5–7 Asahimachi, Abeno-ku, Osaka, Japan (YO, AA) Correspondence to Hiroko Iwakiri, Department of Anesthesiology, Tokyo Women’s Medical University 8–1 Kawadacho, Shinjuku-ku, Tokyo 162–8666, Japan Tel: +81 3 3353 8111; fax: +81 3 3359 2517; e-mail: [email protected] Published online 26 March 2012
Editor, This prospective, randomised, double-blind controlled trial was designed to examine the efficacy of low-dose continuous infusion of dexmedetomidine (DEX) on pain/ sedation scores and verify the plasma concentration of DEX in postoperative patients recovering in general wards conditions. Ethics: Ethical approval for this study (Ethical Committee number 547) was provided by the Ethical Committee of Tokyo Women’s Medical University, Tokyo, Japan (Chairperson of the committee was Professor Makio Kobayashi) on 6 July 2004. Thirty-three gynaecological surgery patients with the American Society of Anesthesiologists physical status
of I or II (exclusion criteria included propofol allergy, severe liver and/or renal dysfunction, grade II or III A-V block, severe cardiac dysfunction, regular use of b-blockers and obesity) were allocated in a random and doubleblind manner to a control group (isotonic saline, n ¼ 11), a DEX-loading () group (0.3–0.4 mg kg1 h1 infusion, n ¼ 11) or a DEX-loading (þ) group (initial 1 h 0.9– 1.0 mg kg1 h1, then 0.3–0.4 mg kg1 h1 infusion, n ¼ 11). Blinding of the anaesthesiologists and the evaluators of effects (the ward nurses) was achieved by isolation of DEX syringe preparation by an independent individual. Randomisation was completed by a computergenerated random list, and placing each patient’s group allocation in a sequentially numbered sealed envelope ensured allocation concealment. Finally, patients were enrolled by a trained research nurse. The flowchart of all patients in this study is shown as Figure 1. To provide continuous venous infusion of DEX and physiological saline, a Coodech Syrinjector, a mobile disposable negative-pressure infusion pump (Daiken Medical, Osaka, Japan), was used, primed with a volume of 120 ml to facilitate patient transport to the generalward room and up to 20 h while recuperating. The reason for using the Syrinjector for continuous infusion is that it is not necessary to set up the panel of the pump, as is generally required with an electrical pump. Additionally, using the Syrinjector avoided human errors such as excessive overdosing of the drug when using an electric syringe pump, and therefore we considered it could be used continuously, safely and easily in general wards. Also, we confirmed that the Syrinjector could perform a stable continuous infusion because the DEX plasma concentration remained within a reasonable range. Anaesthesia was induced and maintained with propofol and fentanyl. The fentanyl effect-site concentration was calculated with a handheld computer using Shafer’s parameters,1 and was titrated to a final concentration of 1.5–2 ng ml1 at the end of surgery. After the patient recovered from anaesthesia, DEX (10 mg ml1) or isotonic saline as a control was placed in the Syrinjector and a flow rate of 5 ml h1 was selected for loading then 2 ml h1 in DEX-loading (þ) group, or 2 ml h1 only in DEX-loading () group. The infusion was connected to one of the peripheral intravenous lines. Verbal Response Scale (VRS) for pain, Ramsay Score, and total doses of sedative/analgesic drugs, mean blood pressure (MBP), heart rate (HR), SpO2 and respiratory rate were recorded on awakening from anaesthesia, entering the post anaethesia care unit, and 0.5, 1, 1.5, 2, 3, 4, 7, 10, 13, 16 and 19 h after starting the infusion. The number of patients in each group was determined by a preliminary study using power analysis of variance (ANOVA) with ‘R’ version 2.6.0. [In that study, the VRS decreased from 4.7 1.0 to 2.6 1.2 between the control group and the DEX-loading () group.] Power analysis on the assumption of type 1 error protection of 0.05 and a power of European Journal of Anaesthesiology
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Fig. 1
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Flowchart of this study profile. DEX, dexmedetomidine; PACU, post-anaesthesia care unit.
0.90 to detect a 2-number reduction in the VRS between the DEX groups and the control group showed that 11 patients were required for each of the three groups receiving DEX or physiological saline. Data are presented as mean SD and for statistical analysis, repeated measures of ANOVA with Tukey post-hoc test were performed with a 0.05 two-sided significance level. To evaluate the DEX infusion speed, we analysed the plasma concentration of DEX 1 and 10 h after starting the infusion using high performance liquid chromatographymass spectrometry (LC-MS) as reported previously, with small modifications. Briefly, DEX was extracted with a solid-phase column (Oasis HLB, 30 mg ml1 Waters, Massachusetts) and measured with tandem mass-spectrometry using 100 ng of midazolam as an internal standard (4000 Qtrap, Analytical Biosystems, Foster City, California, USA). The within-day and day-to-day coefficients of variance were 7.5 and 8.2%, respectively, at 0.1 ng ml1 and 3.5 and 4.2%, respectively, at 1.0 ng ml1. The limit of detection was 0.02 ng ml1. The demographic parameters observed were similar in the three groups. Throughout the study period, the changes in the values of SpO2 and respiratory rate were not significant among the groups and these parameters remained within normal limits (SpO2 >96% without any oxygen supplementation and respiratory rate >8 breaths min1). The amount of DEX administered during 1 h loading from the start of the infusion was 0.93 0.14 mg kg1 h1 in the DEX-loading (þ) group
and subsequently 0.37 0.06 mg kg1 h1. In contrast, it was 0.37 0.04 mg kg1 h1 in the DEX-loading () group throughout the course of the study. The VRS during the observation period in the DEX-loading (þ) group, the DEX-loading () group and the control group averaged 2.3 0.5, 2.3 0.6 and 4.3 0.4, respectively. Thus, a significantly lower VRS was recorded in both DEX groups than in the control group (P < 0.05). The VRS value difference between the DEX-loading (þ) and DEX-loading () group was insignificant. The VRS values are shown in Figure 2. The mean Ramsay Scores in the DEX-loading (þ) group, the DEX-loading () group and the control group were 2.2 0.1, 2.1 0.1 and 2.2 0.1, respectively. No significant differences were observed among the three groups. The average HR value throughout the study period was 62 3 beats min1 in the DEX-loading (þ) group, 68 2 beats min1 in the DEX-loading () group, and 72 3 beats min1 in the control group. The HR of the patients in the DEXloading (þ) group was significantly lower than in the control group, at some points. The MBP was significantly lower in the DEX groups (P < 0.01). There were no significant haemodynamic differences between the DEX-loading (þ) and loading () groups during the study period. Haemodynamic instability, defined as requiring treatment, was not observed throughout the study. The total dose of pentazocine administered for acute pain relief was significantly lower in both the DEX groups than in the control group (P < 0.05) and a significantly lower dose of hydroxyzine was used as a sedative in both of the DEX groups compared to the control group
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Fig. 2
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Elapsed time (h) Patient-rated verbal response scales (VRS; 0–10) for level of pain during a continuous infusion of dexmedetomidine (DEX) or saline (control). 0 indicated no pain and 10 excruciating pain. In both DEX groups, VRS scores were significantly lower than in the control group (P < 0.01 and P < 0.05).
(Figure 3). Hydroxyzine was used for sedation when the Ramsay score was less than 2, and pentazocine was used for analgesia when the VRS was over 5. As shown in Figure 3, the total amount of hydroxyzine used in the control group was significantly higher than the DEX groups and as a result caused similar sedative status
as indicated by the Ramsay score regardless of the analgesic status, which was significantly different from the DEX groups. The DEX plasma concentration in the DEX-loading (þ) group 1 h after starting the infusion was 0.64 0.22 ng ml1, and after 10 h it was 0.46 0.13 ng ml1. In the DEX-loading () group the
Fig. 3
Sedative/analgesic drugs mg PS DEX-loading (+) DEX-loading (−)
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The mean total dosage (mg) of sedative/analgesic drugs during a continuous infusion of dexmedetomidine (DEX) or saline (control). The doses of both pentazocine and hydroxyzine were significantly lower in the DEX groups than in the control group (P < 0.05).
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254 Correspondence
corresponding values were 0.20 0.05 ng ml1 and 0.45 0.14 ng ml1.
invasive, it might be necessary to titrate the DEX infusion rate.
DEX provides an important degree of postsurgical analgesia and appears to have no clinically important adverse effects on respiration in surgical patients requiring intensive care or in healthy volunteers.2–4 This limited respiratory effect is considered to be an advantage of DEX in terms of general ward use. Despite these advantages, the fact that DEX induces cardiovascular sideeffects5 which might lead to haemodynamic instability, such as hypertension, hypotension and bradycardia, could be a problem for using DEX in general wards. Therefore, careful consideration should be given to the decision to administer DEX. To use DEX in the general ward safely, only appropriate concentrations should be used, and extra care should be taken when using higher concentrations. The clinically effective plasma concentration of DEX is reported to range from 0.3 to 1.2 ng ml1. In this study, we obtained approximately 0.45 ng ml1 plasma concentration of DEX 10 h after starting the infusion in both DEX groups. This was confirmed to be a clinically relevant effective plasma concentration. However, when we evaluated the plasma concentration 1 h after starting the DEX infusion, it was 0.64 ng ml1 in the DEX-loading (þ) group, whereas it was 0.20 ng ml1 in the DEXloading () group, the latter of which was below the clinically effective concentration. On the contrary, rapid loading of DEX might induce excessive systemic hypertension,6,7 so in this study, DEX was loaded for 1 h very slowly and, therefore, no excessive hypertension occurred.
In conclusion, DEX administered with this infusion method provided significantly lower VRS values without clinically problematic side-effects. We also confirmed clinically effective DEX plasma concentrations. For the reasons discussed above, we consider this low-dose DEX continuous infusion method to be useful for postoperative management after gynaecological surgery, even in general wards.
A limitation of our study was that the patients who received DEX postoperatively had only gynaecological surgery in the lower abdominal region. If the area of the surgery was greater, or when the operation becomes more
7
Acknowledgements The authors gratefully acknowledge the assistance of nursing staff in PACU and the gynaecological general ward. We had institutional (Department of Anesthesiology) funding only for this work. None of the authors has any conflicts of interest.
References 1
2
3
4
5 6
Shafer SL, Varvel JR, Aziz N, Scott JC. Pharmacokinetics of fentanyl administered by computer-controlled infusion pump. Anesthesiology 1990; 73:1091–1102. Venn RM, Bradshaw CJ, Spencer R, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999; 54:1136–1142. Venn RM, Grounds RM. Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth 2001; 87:684–690. Hsu YW, Cortinez LI, Robertson KM, et al. Dexmedetomidine pharmacodynamics: part I – crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 2004; 101:1066–1076. Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000; 93:1345–1349. Ebert TJ, Hall JE, Barney JA, et al. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000; 93:382–394. Talke P, Lobo E, Brown R. Systemically administered alpha2-agonistinduced peripheral vasoconstriction in humans. Anesthesiology 2003; 99:65–70. DOI:10.1097/EJA.0b013e3283529ba8
European Journal of Anaesthesiology 2012, Vol 29 No 5
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ECG changes during in-situ hypothermic liver resections Francois M. Carrier, Claudia Tanase, Salima Naili, Tonine Bartelmaos, Daniel Azoulay and Dan Benhamou From the Centre Hospitalier de l’Universite´ de Montre´al, Montreal, Quebec, Canada (FMC), Department of Anaesthesiology (FMC, CT, SN, TB, DB) and Department of Hepato-Biliary Surgery, Hoˆpital Paul-Brousse (DA), Villejuif, France Correspondence to Francois M. Carrier, MD, Department of Anaesthesiology, Hopital Paul-Brousse, 12–14 Avenue Paul-Vaillant-Couturier, 94804 Villejuif, France Tel: +33 1 4559 3219; fax: +33 1 4559 3834; e-mail: [email protected] Published online 28 October 2011
Editor, Liver resection is increasingly performed to remove colorectal metastases.1 It provides clinical benefits through complete resection of the neoplastic material.2 Surgical techniques are improving to extend this therapy to more patients and complex situations.3 When major resection with vascular reconstruction is deemed necessary, in-situ hypothermic liver resection becomes an option. It is thought to better preserve liver function when a long ischemic time is needed for parenchyma resection and vascular reconstruction.4 To decrease liver temperature, a topical cooling technique can be used alone or with portal hypothermic perfusion. Such techniques have major implications for the anaesthesiologist, such as potential hemodynamic instability, coagulopathy, hypothermia and hyperkalaemia.5 This article describes the occurrence of ECG changes that were observed during two major liver resections while using a topical cooling technique. When we started using hypothermic liver resection in our centre, liver hypothermia was achieved with topical cooling only. During two of these cases, unexpected ECG changes were observed. The first patient, a 43-year-old man without specific past medical history, was scheduled for open right hepatectomy. After dissection, topical cooling of the liver was induced by placing wet icy cold gauzes both in the retro-hepatic space and over the superior border of the liver. When the surgeon mobilised the liver to start the resection, cold gauzes inserted over the superior border of the liver came into contact with the diaphragm. The patient then developed ST segment depression and profound T wave inversion on DII and V5 derivations. These changes rapidly disappeared when the gauzes were removed, but reappeared quickly after the gauzes were reinserted. Figure 1a shows the preoperative ECG. Figure 1b shows ECG changes 2 min following gauze placement. Figure 1c shows the ECG
immediately after removal of the gauzes. A couple of minutes later, the same changes were observed when the gauzes were reinserted in the same space (Fig. 1d). The gauzes placed over the superior border of the liver were then completely removed. A couple of months later, the same changes were observed in a 51-year-old man just after the gauzes over the superior border of the liver had been placed. On the basis of our previous experience, the gauzes were rapidly removed and the ECG normalised (not shown). As the ECG changes were rapidly detected, the contact time between the gauzes and the diaphragm lasted only few minutes. In neither of these patients arrhythmias or hemodynamic instability were noted. Changes (if any) of cardiac function could not be demonstrated, as a transesophageal echocardiography probe was not inserted and not available at the time of the events. The use of cold gauzes over the superior border of the liver during in-situ hypothermic liver resection with topical cooling seems to induce ECG changes. As the liver is very close to the right ventricle, a local effect on epicardial repolarisation might explain the observed changes.6 This technique could have also induced a return of cold blood to the right ventricle, similar to that observed during orthotopic liver transplantation. However, significant temperature changes deep inside the liver might well take a few minutes under topical cooling. ECG changes were observed seconds after placement of gauzes and started to recede very soon after their removal, suggesting a local effect. Indeed, similar but more sustained ECG changes due to possible hypothermic–osmotic damages have been reported in paediatric cardiac patients after topical cooling of the heart with ice.7 In our patients, both the short contact time and the relative protection of the heart offered by the diaphragm likely prevented sustained changes such as arrhythmia or hemodynamic instability. To our knowledge, this is the first report of ECG changes due to local cardiac cooling during non-cardiac surgery. After these observations were made, the cooling technique was modified and cold gauzes placed above the liver are now separated from the diaphragm by gauzes at ambient temperature. Moreover, we now use an intrahepatic cooling technique with portal hypothermic perfusion of the liver that depends less on the use of cold gauzes. When performing this technique, a porto-venovenous bypass is first inserted and then both the retrohepatic space and the superior border of the liver are packed with icy cold gauzes as described above. Total liver vascular exclusion is performed and cold graft preservation solution is infused through the portal vein and
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Fig. 1
6 7
Azarov JE, Shmakov DN, Vityazev VA, et al. Ventricular repolarization pattern under heart cooling in the rabbit. Acta Physiol 2008; 193:129–138. Corno A, Zoia E, Santoro F, et al. Epicardial damage induced by topical cooling during paediatric cardiac surgery. Br Heart J 1992; 67:174–176. DOI:10.1097/EJA.0b013e32834d86d8
Bilateral bispectral index differences in asymptomatic internal carotid stenosis (a) Basal ECG. (b) ECG after placement of cold gauzes. (c) ECG immediately after removal of gauzes. (d) ECG after the gauzes were reinserted in the same space.
Marı´a J. Estruch-Pe´rez, Juan Soliveres-Ripoll, Josep BalaguerDomenech, Lorena Go´mez-Diago, Alicia Sanchez-Hernandez and Cristina Solaz-Rolda´n From the Anaesthesiology and Critical Care Department, Dr Peset University Hospital, Valencia, Spain (MJEP, JSR, JBD, LGD, ASH, CSR)
drained from a retro-hepatic cavotomy. When surgery is completed, the preservation solution is flushed and the bypass weaned. In our experience, this technique is associated with a lower systemic temperature and a more sudden return of cold blood after unclamping. Nevertheless, no profound ECG changes such as those described previously have been observed with the modified technique which is consistent with a local effect hypothesis. Moreover, portal hypothermic perfusion is not only associated with an intra-hepatic cooling effect which depends less on topical gauzes, but it is the only technique that has been associated with improved clinical outcome.4,5 We suggest that during in-situ hypothermic liver resection, cold gauzes over the superior border of the liver should be separated from the diaphragm to avoid the occurrence of ECG changes. Moreover, a portal hypothermic perfusion technique might be preferred.
Acknowledgements The authors would like to thank Dr Marie-Christine Gillon for her assistance in data retrieval and Miss Nadia Morfousse for her clerical work. The Royal College of Physicians and Surgeons of Canada supported this work by a fellowship grant. None of the authors has any conflict of interest.
References 1
2
3 4
5
Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009; 27:3677–3683. Wei AC, Greig PD, Grant D, et al. Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol 2006; 13:668–676. Berri RN, Abdalla EK. Curable metastatic colorectal cancer: recommended paradigms. Curr Oncol Rep 2009; 11:200–208. Azoulay D, Eshkenazy R, Andreani P, et al. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg 2005; 241:277–285. DuBay D, Gallinger S, Hawryluck L, et al. In situ hypothermic liver preservation during radical liver resection with major vascular reconstruction. Br J Surg 2009; 96:1429–1436.
Correspondence to Marı´a J. Estruch Pe´rez, MD, Anesthesiology and Critical Care Department, Dr Peset University Hospital, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain E-mail: [email protected] Published online 10 January 2012
Editor, An unexpected bispectral index (BIS) decrease may indicate inadequate cerebral perfusion.1 Further, BIS may be useful for monitoring carotid artery disease.2,3 Differences in BIS values from two electrodes applied simultaneously to the same patient have been reported.4 We describe a patient who, while under simultaneous bilateral BIS monitoring, suffered a right-side fall in BIS values. A hypertensive, 72-year-old male patient underwent bilateral inguinal hernia repair under local anaesthesia and deep sedation. We obtained the patient’s explicit consent to publish his data in this case report. After standard monitoring, continuous three-lead ECG, continuous SpO2 and 5 min interval blood pressure determinations were recorded. Two BIS quattro sensors (Covidien, Medical, Boulder, CO, USA) were applied to each side of the forehead (right and left) and connected to two BIS Vista monitors (Covidien) as part of a clinical trial. Clocks on the two monitors were synchronised just before monitoring the patient. Bilateral BIS readings were recorded every minute. A unique bolus of 0.1 mg fentanyl and 160 mg propofol was intravenously administered, followed by a 6 mg kg1 h1 continuous propofol infusion. No additional medication was given. A laryngeal mask was placed and 50% oxygen in air spontaneous breathing was allowed. Field block was performed using 20 ml 1% mepivacaine. After 10 min, the suppression ratio began to increase progressively, especially on the right side. No mean blood pressure change was observed. After 20 min, BIS values from the right electrode suddenly decreased and the European Journal of Anaesthesiology
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248 Correspondence
Fig. 1
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Minute Changes in values of bispectral index (BIS), in suppression ratio (SR) and non invasive blood pressure values (NIBP) during the whole surgery. NIBP determinations (mmHg) can be read from each vertical bar. SBP (top of the bar), mean blood pressure (middle) and DBP (bottom) are shown. L-BIS, left-side BIS; R-BIS, right-side BIS; L-SR, left BIS suppression ratio; R-SR, right BIS suppression ratio.
suppression ratio of the right electrode increased simultaneously (Fig. 1). A manually started blood pressure determination showed hypotensive blood pressure values; thus, propofol infusion was stopped and 100% oxygen was administered and blood pressure was increased using volume expanders. There were no concomitant changes in the other standard monitoring values. Eight minutes later, blood pressure had returned to previous values despite the right-side BIS value remaining lower than the left one for almost 20 min. A correlation between blood pressure and BIS difference could be observed.
Fig. 2
By the time the patient emerged from deep sedation, the two BIS values were not significantly different. Postoperative course was uneventful. No intraoperative awareness was found. As the neurological examination was normal (done by the anaesthesiologist), unilateral transient ischaemia was suspected. No further cerebral image diagnostic tests were made. As carotid echo Doppler test is highly available, it showed a right carotid stenosis. The arteriography revealed over 70% right stenosis (Fig. 2). The patient was scheduled for right carotid stent placement. The asymmetric BIS values alerted us to a possible vascular incident with concomitant cerebral ischaemia leading to permanent low BIS values of the right-sided electrode.
Arteriography of the carotid stenosis.
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Correspondence 249
BIS value changes can be observed during periods at risk of cerebral hypoperfusion, such as the carotid crossclamping period.2,3 These findings need further studies to be conclusive. A 70-year-old patient with bilateral internal carotid artery stenosis was reported to have shown a sudden BIS value asymmetry after temporary bypass during a left carotid endarterectomy, as a sign of reperfusion. In the second operation for the right side, no marked discrepancy between the two sides was observed.5 In cases of internal carotid stenosis, discrepancies in BIS and state entropy values have also been seen during general surgery.6,7 The decrease in the BIS signal observed in our patient could indicate a low right frontal cortical activity, assumably due to cerebral hypoperfusion caused by a considerable decrease in blood pressure. However, blood pressure returned to previous levels, whereas the BIS asymmetry remained until the end of surgery. The large and unexpected decrease in BIS values made us think about an ischaemic event or inadequate cerebral perfusion as a result of a carotid stenosis, as it has been reported previously during carotid surgery.5–7 Although small discrepancies in BIS values from sensors placed on each side of the forehead are recognised as normal, a unilateral decrease in BIS values should be considered important and investigated, especially in patients with cardiovascular risk factors, as it can be an indicator of asymptomatic internal carotid stenosis. The timely diagnosis of cerebral hypoperfusion during general anaesthesia is not only limited to an EEG specialist, but may be achieved by the attendant anaesthesiologist as well.
Acknowledgement There are no financial supports or sponsorships or conflicts of interest or assistance with the study to declare.
References 1
2
3
4 5
6
7
Morimoto Y, Monden Y, Ohtake K, et al. The detection of cerebral hypoperfusion with bispectral index monitoring during general anesthesia. Anesth Analg 2005; 100:158–161. Estruch-Pe´rez MJ, Barbera´-Alacreu M, Ausina-Aguilar A, et al. Bispectral index variations in patients with neurological deficits during awake carotid endarterectomy. Eur J Anaesthesiol 2010; 27:359–363. Bonhomme V, Quentin D, Thierry L, et al. Bispectral index profile during carotid cross clamping. J Neurosurg Anesthesiol 2007; 19:49–55. Niedhart DJ, Kaiser HA, Jacobsohn E, et al. Intrapatient reproducibility of the BISxp monitor. Anesthesiology 2006; 104:242–248. Kodaka M, Nishikawa Y, Suzuki T, et al. Does bilateral bispectral index monitoring (BIS) detect the discrepancy of cerebral reperfusion during carotid endarterectomy? J Clin Anesth 2009; 21:431–434. Lee EH, Choi IC, Song JG, et al. Different bispectral index values from both sides of the forehead in unilateral carotid artery stenosis. Acta Anaesthesiol Scand 2009; 53:134–136. Khan QS, Ozcan MS. Disagreement in bilateral state entropy values in carotid artery disease. J Neurosurg Anesthesiol 2011; 23:51–52. DOI:10.1097/EJA.0b013e32834f5f26
Datex-Ohmeda NeuroMuscular Transmission electromyography module artefacts in clinical practice: case report and retrospective chart review Philippe E. Dubois, John Mitchell, Christophe Dransart and Alain d’Hollander From the Department of Anaesthesiology, University of Louvain, CHU MontGodinne, Yvoir, Belgium (PED, JM, CD) and Department of Anaesthesiology, University Hospital, Geneva, Switzerland (Ad’H) Correspondence to Dr Philippe E. Dubois, Department of Anaesthesiology, CHU Mont-Godinne, 1 Avenue Therasse, B-5530 Yvoir, Belgium Tel: +32 81423929; fax: +32 81423920; e-mail: [email protected] Published online 1 March 2012
Editor, Inducing a neuromuscular block (NMB) has advantages for the anaesthetist and the surgeon, but exposes the patient to the risk of residual curarisation.1 This can be reduced using various methods of quantitative NMB monitoring.2 The NeuroMuscular Transmission Module (M-NMT) (GE Healthcare, Hatfield, UK; formerly Datex-Ohmeda, Helsinki, Finland) uses kinemyography or electromyography (EMG). The module can record and display data throughout the period of NMB and save the data in the anaesthesia record (AS/5 monitor Gangwon-do, Korea). EMG measures muscle electrical activity using surface electrodes that can be easily attached to the hand, among other sites. The EMG responses are acknowledged to be consistent over time and less sensitive to changes in the position of the hand than acceleromyography3 and, probably, less than kinemyography.4 Given these advantages, continuous quantitative monitoring of NMB by EMG has gradually been adopted in clinical practice in our institution. Unfortunately, numerous recordings provided illogical trends of the NMB. To illustrate the aberrant results provided by the device in some clinical cases, we report data obtained from a 95-kg patient who underwent abdominal surgery under general anaesthesia (Fig. 1). EMG monitoring was started in operating room according to the Datex-Ohmeda Neuromuscular monitoring guide5 and in accordance with good clinical practice.6 The stimulating electrodes (E152, IMMED, Bio Protech Inc., Gangwon-do, Korea) were applied to the wrist over the ulnar nerve. The recording electrode was placed on the thenar eminence over the belly of the adductor pollicis muscle and the indifferent electrode was placed on the first phalanx of the thumb. The neutral ground electrode was placed over the carpal ligament on the inner surface of the wrist. The automatic calibration sequence was completed before administering rocuronium by searching for the supramaximal stimulation level and 100% calibration of twitch height (T1). This was followed by 2-Hz train-of-four (TOF) stimulations every 20 s, with the EMG responses (TOF count, T1 and TOF ratio) recorded online. European Journal of Anaesthesiology
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250 Correspondence
Fig. 1 roc 50 mg
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The Datex-Ohmeda NeuroMuscular Transmission Module (M-NMT) windows during a neuromuscular block monitored by electromyography (EMG) as displayed on the AS/5 anaesthesia monitor. (a) The trends window is shown. The first twitch height (T1) is represented as a percentage of the initial calibration by dots; the train-of-four (TOF) count is represented by crosses and the TOF ratio (T4/T1) is represented as a percentage by vertical lines. The thick black line indicates the time of recording of the data (b and c). (b) The four EMG responses with reference to the EMG from the initial calibration (in grey) are shown. (c) The numeric values for TOF ratio, TOF count and T1 are shown.
Shortly after administering rocuronium 50 mg, four small responses reappeared on the screen in response to the TOF stimulations. The calculated TOF ratio was more than 0.9. Surprisingly, this figure fell gradually as the T1 height increased. The EMG responses did not disappear after further boluses of rocuronium 10 mg, and the TOF ratio remained high until surgery ended. Sugammadex 200 mg enabled rapid recovery of four responses with T1 more than 100% and without fade (TOF ratio > 0.9) and made it possible to extubate the patient in the absence of residual block. The main problem was the unexpected recording of the four small responses that persisted during deep and moderate blockade (Fig. 1b). Only two actual muscular EMG responses were recorded within the four identical artefacts. However, the device interpreted them as four real twitches (T1: 12% and TOF count: 4; Fig. 1c). The TOF ratio was inappropriately calculated (83%, GE Healthcare) and increased after further administration of rocuronium. To determine how frequently this problem arises in our clinical practice, we carried out a chart review to objectively assess the quality of the EMG recordings provided by the Datex-Ohmeda M-NMT module. Following Institutional Ethics Committee approval (CHU MontGodinne om 050, 69/2011), 100 EMG recordings of nondepolarising NMB randomly selected over a period of 1 year were analysed retrospectively. The patients’ mean (SD) age was 51 (19) years and BMI was 26 (5) kg m2 and they underwent various types of surgery. Rocuronium 0.48 (0.11), atracurium 0.45 (0.10) and cisatracurium 0.13 (0.05) mg kg were administered to 68, 30 and two patients, respectively. Neostigmine was administered in 45% of cases.
The initial EMG was properly calibrated in 72 cases. Taking into account whether or not the initial calibration was carried out, the quality of various aspects of the EMG recordings was assessed: the capacity to determine the TOF count gradually (from 1 to 4) – 82 and 54% of cases, respectively; whether the early trend of TOF ratio was considered consistent (gradually increasing from an initial level <50%, and inter-measurement variability <15%) – 34 and 25% of cases, respectively; and, conversely, if the TOF ratio’s final assessment was consistent – in 91 and 71% of cases, respectively. We have shown that when using the M-NMT DatexOhmeda module, problems may exist regarding the interpretation of the EMG recordings to the point where this limited their usefulness in managing the NMB. In particular, the detection of four small, almost identical EMG responses shortly after the induction of the block resulted in an incorrect calculation of a TOF count and a high TOF ratio. This problem frequently led to the false assumption that the patient was not completely paralysed (up to 75% of cases in the absence initial calibration). The presence of these small responses without fade during deep block was previously attributed to direct muscular stimulation. However, recent studies have shown that the current used in NMB monitoring (pulse duration 0.2 ms, intensity 10–60 mA) was usually inadequate to induce genuine muscular stimulations.7 Thus, other reasons specific to the method of EMG recording used by the Datex-Ohmeda M-NMT module probably contributed to the artefactual detection of these small responses. Further prospective investigation should be undertaken to determine the cause. During NMB recovery, as ‘real’ twitches appear and then increase, they replace the artefacts and the calculated TOF ratio decreases progressively (as the real twitches exhibit fade), before increasing again until as fade disappears towards the end of recovery (Fig. 1a). The quality of the TOF ratio measurements increased with the intensity of the muscular responses recorded, reducing the impact of artefacts at the end of the case. However, in 29% of cases when initial calibration had not been performed, it was not possible to rule out residual curarisation before the patient awoke. We have shown that the recordings were of a better quality when calibration was undertaken prior to administering rocuronium. Even if artefacts remain, it seems useful to calibrate the initial twitches to limit the magnitude of electrical interference during the recording of the muscular responses. In conclusion, artefacts alter EMG recordings provided by the Datex-Ohmeda M-NMT module, particularly during deep and moderate block. Additional technical improvements are needed to guarantee clinicians correct management of NMB in all patients.
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Correspondence 251
Acknowledgements This work was supported by departmental funds. A.d’.H. is a non-remunerated consultant and board member of Medical Devices Bio Engineering-sprl, Waterloo, Belgium.
References 1
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Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part 1. Definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg 2010; 111:120–128. Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II. Methods to reduce the risk of residual weakness. Anesth Analg 2010; 111:129–140. Ha¨nzi P, Leibundgur D, Wessendorf R, et al. Clinical validation of electromyography and acceleromyography as sensors for muscle relaxation. Eur J Anaesthesiol 2007; 24:882–888. Dahaba AA, Von Klobucar F, Rehak PH, List WF. The neuromuscular transmission module versus the relaxometer mechanomyograph for neuromuscular block monitoring. Anesth Analg 2002; 94:591–596. Brull SJ, Paloheimo M. A practical guide to monitoring neuromuscular function. Datex-Ohmeda Division Instrumentarium Corp. Helsinki, Finland; 2002. Fuchs-Buder T, Claudius C, Skovgaard LT, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007; 51:789–808. Kopman AF. Can conventional peripheral nerve stimulators induce direct muscle depolarization? Anesth Analg 2006; 102:1905. DOI:10.1097/EJA.0b013e32834f8f76
The efficacy of continuous infusion of low dose dexmedetomidine for postoperative patients recovering in general wards Hiroko Iwakiri, Yutaka Oda, Akira Asada and Makoto Ozaki From the Department of Anesthesiology, Tokyo Women’s Medical University 8–1 Kawadacho, Shinjuku-ku, Tokyo, (HI, MO) and Department of Anesthesiology, Osaka City University Graduate School of Medicine 1–5–7 Asahimachi, Abeno-ku, Osaka, Japan (YO, AA) Correspondence to Hiroko Iwakiri, Department of Anesthesiology, Tokyo Women’s Medical University 8–1 Kawadacho, Shinjuku-ku, Tokyo 162–8666, Japan Tel: +81 3 3353 8111; fax: +81 3 3359 2517; e-mail: [email protected] Published online 26 March 2012
Editor, This prospective, randomised, double-blind controlled trial was designed to examine the efficacy of low-dose continuous infusion of dexmedetomidine (DEX) on pain/ sedation scores and verify the plasma concentration of DEX in postoperative patients recovering in general wards conditions. Ethics: Ethical approval for this study (Ethical Committee number 547) was provided by the Ethical Committee of Tokyo Women’s Medical University, Tokyo, Japan (Chairperson of the committee was Professor Makio Kobayashi) on 6 July 2004. Thirty-three gynaecological surgery patients with the American Society of Anesthesiologists physical status
of I or II (exclusion criteria included propofol allergy, severe liver and/or renal dysfunction, grade II or III A-V block, severe cardiac dysfunction, regular use of b-blockers and obesity) were allocated in a random and doubleblind manner to a control group (isotonic saline, n ¼ 11), a DEX-loading () group (0.3–0.4 mg kg1 h1 infusion, n ¼ 11) or a DEX-loading (þ) group (initial 1 h 0.9– 1.0 mg kg1 h1, then 0.3–0.4 mg kg1 h1 infusion, n ¼ 11). Blinding of the anaesthesiologists and the evaluators of effects (the ward nurses) was achieved by isolation of DEX syringe preparation by an independent individual. Randomisation was completed by a computergenerated random list, and placing each patient’s group allocation in a sequentially numbered sealed envelope ensured allocation concealment. Finally, patients were enrolled by a trained research nurse. The flowchart of all patients in this study is shown as Figure 1. To provide continuous venous infusion of DEX and physiological saline, a Coodech Syrinjector, a mobile disposable negative-pressure infusion pump (Daiken Medical, Osaka, Japan), was used, primed with a volume of 120 ml to facilitate patient transport to the generalward room and up to 20 h while recuperating. The reason for using the Syrinjector for continuous infusion is that it is not necessary to set up the panel of the pump, as is generally required with an electrical pump. Additionally, using the Syrinjector avoided human errors such as excessive overdosing of the drug when using an electric syringe pump, and therefore we considered it could be used continuously, safely and easily in general wards. Also, we confirmed that the Syrinjector could perform a stable continuous infusion because the DEX plasma concentration remained within a reasonable range. Anaesthesia was induced and maintained with propofol and fentanyl. The fentanyl effect-site concentration was calculated with a handheld computer using Shafer’s parameters,1 and was titrated to a final concentration of 1.5–2 ng ml1 at the end of surgery. After the patient recovered from anaesthesia, DEX (10 mg ml1) or isotonic saline as a control was placed in the Syrinjector and a flow rate of 5 ml h1 was selected for loading then 2 ml h1 in DEX-loading (þ) group, or 2 ml h1 only in DEX-loading () group. The infusion was connected to one of the peripheral intravenous lines. Verbal Response Scale (VRS) for pain, Ramsay Score, and total doses of sedative/analgesic drugs, mean blood pressure (MBP), heart rate (HR), SpO2 and respiratory rate were recorded on awakening from anaesthesia, entering the post anaethesia care unit, and 0.5, 1, 1.5, 2, 3, 4, 7, 10, 13, 16 and 19 h after starting the infusion. The number of patients in each group was determined by a preliminary study using power analysis of variance (ANOVA) with ‘R’ version 2.6.0. [In that study, the VRS decreased from 4.7 1.0 to 2.6 1.2 between the control group and the DEX-loading () group.] Power analysis on the assumption of type 1 error protection of 0.05 and a power of European Journal of Anaesthesiology
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252 Correspondence
Fig. 1
Continuous infusion start
DEX-loading(+) 0.9~1.0 µg kg−1 h−1
Blood sampling
Blood sampling
1h
10 h
Continuous infusion finish
20 h
03~0.4 µg kg−1 h−1
DEX-loading(−) 03~0.4 µg kg−1 h−1 Saline (as a control)
Awake from anaesthesia (operation room)
PACU
General ward
Flowchart of this study profile. DEX, dexmedetomidine; PACU, post-anaesthesia care unit.
0.90 to detect a 2-number reduction in the VRS between the DEX groups and the control group showed that 11 patients were required for each of the three groups receiving DEX or physiological saline. Data are presented as mean SD and for statistical analysis, repeated measures of ANOVA with Tukey post-hoc test were performed with a 0.05 two-sided significance level. To evaluate the DEX infusion speed, we analysed the plasma concentration of DEX 1 and 10 h after starting the infusion using high performance liquid chromatographymass spectrometry (LC-MS) as reported previously, with small modifications. Briefly, DEX was extracted with a solid-phase column (Oasis HLB, 30 mg ml1 Waters, Massachusetts) and measured with tandem mass-spectrometry using 100 ng of midazolam as an internal standard (4000 Qtrap, Analytical Biosystems, Foster City, California, USA). The within-day and day-to-day coefficients of variance were 7.5 and 8.2%, respectively, at 0.1 ng ml1 and 3.5 and 4.2%, respectively, at 1.0 ng ml1. The limit of detection was 0.02 ng ml1. The demographic parameters observed were similar in the three groups. Throughout the study period, the changes in the values of SpO2 and respiratory rate were not significant among the groups and these parameters remained within normal limits (SpO2 >96% without any oxygen supplementation and respiratory rate >8 breaths min1). The amount of DEX administered during 1 h loading from the start of the infusion was 0.93 0.14 mg kg1 h1 in the DEX-loading (þ) group
and subsequently 0.37 0.06 mg kg1 h1. In contrast, it was 0.37 0.04 mg kg1 h1 in the DEX-loading () group throughout the course of the study. The VRS during the observation period in the DEX-loading (þ) group, the DEX-loading () group and the control group averaged 2.3 0.5, 2.3 0.6 and 4.3 0.4, respectively. Thus, a significantly lower VRS was recorded in both DEX groups than in the control group (P < 0.05). The VRS value difference between the DEX-loading (þ) and DEX-loading () group was insignificant. The VRS values are shown in Figure 2. The mean Ramsay Scores in the DEX-loading (þ) group, the DEX-loading () group and the control group were 2.2 0.1, 2.1 0.1 and 2.2 0.1, respectively. No significant differences were observed among the three groups. The average HR value throughout the study period was 62 3 beats min1 in the DEX-loading (þ) group, 68 2 beats min1 in the DEX-loading () group, and 72 3 beats min1 in the control group. The HR of the patients in the DEXloading (þ) group was significantly lower than in the control group, at some points. The MBP was significantly lower in the DEX groups (P < 0.01). There were no significant haemodynamic differences between the DEX-loading (þ) and loading () groups during the study period. Haemodynamic instability, defined as requiring treatment, was not observed throughout the study. The total dose of pentazocine administered for acute pain relief was significantly lower in both the DEX groups than in the control group (P < 0.05) and a significantly lower dose of hydroxyzine was used as a sedative in both of the DEX groups compared to the control group
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Correspondence 253
Fig. 2
VRS
Saline
10
DEX-loading (+)
9
DEX-loading (−)
8 P < 0.05 DEX-loading (+) vs. control
7
*
6
# P < 0.05 DEX-loading (−) vs. control
5 4 3
#
*
2
*
#
*
1
*
#
#
#
*
* #
#
*
0 At PACU 0.5 awake
1
1.5
2
3
4
7
10
13
16
19
Elapsed time (h) Patient-rated verbal response scales (VRS; 0–10) for level of pain during a continuous infusion of dexmedetomidine (DEX) or saline (control). 0 indicated no pain and 10 excruciating pain. In both DEX groups, VRS scores were significantly lower than in the control group (P < 0.01 and P < 0.05).
(Figure 3). Hydroxyzine was used for sedation when the Ramsay score was less than 2, and pentazocine was used for analgesia when the VRS was over 5. As shown in Figure 3, the total amount of hydroxyzine used in the control group was significantly higher than the DEX groups and as a result caused similar sedative status
as indicated by the Ramsay score regardless of the analgesic status, which was significantly different from the DEX groups. The DEX plasma concentration in the DEX-loading (þ) group 1 h after starting the infusion was 0.64 0.22 ng ml1, and after 10 h it was 0.46 0.13 ng ml1. In the DEX-loading () group the
Fig. 3
Sedative/analgesic drugs mg PS DEX-loading (+) DEX-loading (−)
400 350 300 250 200 150
* 100
#
*
#
50 0 Pentazocine
Hydroxyzine P < 0.05 DEX-loading (+) vs. control P < 0.05 DEX-loading (−) vs. control
The mean total dosage (mg) of sedative/analgesic drugs during a continuous infusion of dexmedetomidine (DEX) or saline (control). The doses of both pentazocine and hydroxyzine were significantly lower in the DEX groups than in the control group (P < 0.05).
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254 Correspondence
corresponding values were 0.20 0.05 ng ml1 and 0.45 0.14 ng ml1.
invasive, it might be necessary to titrate the DEX infusion rate.
DEX provides an important degree of postsurgical analgesia and appears to have no clinically important adverse effects on respiration in surgical patients requiring intensive care or in healthy volunteers.2–4 This limited respiratory effect is considered to be an advantage of DEX in terms of general ward use. Despite these advantages, the fact that DEX induces cardiovascular sideeffects5 which might lead to haemodynamic instability, such as hypertension, hypotension and bradycardia, could be a problem for using DEX in general wards. Therefore, careful consideration should be given to the decision to administer DEX. To use DEX in the general ward safely, only appropriate concentrations should be used, and extra care should be taken when using higher concentrations. The clinically effective plasma concentration of DEX is reported to range from 0.3 to 1.2 ng ml1. In this study, we obtained approximately 0.45 ng ml1 plasma concentration of DEX 10 h after starting the infusion in both DEX groups. This was confirmed to be a clinically relevant effective plasma concentration. However, when we evaluated the plasma concentration 1 h after starting the DEX infusion, it was 0.64 ng ml1 in the DEX-loading (þ) group, whereas it was 0.20 ng ml1 in the DEXloading () group, the latter of which was below the clinically effective concentration. On the contrary, rapid loading of DEX might induce excessive systemic hypertension,6,7 so in this study, DEX was loaded for 1 h very slowly and, therefore, no excessive hypertension occurred.
In conclusion, DEX administered with this infusion method provided significantly lower VRS values without clinically problematic side-effects. We also confirmed clinically effective DEX plasma concentrations. For the reasons discussed above, we consider this low-dose DEX continuous infusion method to be useful for postoperative management after gynaecological surgery, even in general wards.
A limitation of our study was that the patients who received DEX postoperatively had only gynaecological surgery in the lower abdominal region. If the area of the surgery was greater, or when the operation becomes more
7
Acknowledgements The authors gratefully acknowledge the assistance of nursing staff in PACU and the gynaecological general ward. We had institutional (Department of Anesthesiology) funding only for this work. None of the authors has any conflicts of interest.
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