Intraoperative Intravenous Lidocaine Reduces Hospital Length of Stay

Journal of Clinical Anesthesia (2012) 24, 465–470

Original Contribution Intraoperative intravenous lidocaine reduces hospital length of stay following open gastrectomy for stomach cancer in men☆ Jin Gu Kang MD (Clinical Professor), Myung Hee Kim MD, PhD (Professor)⁎, Eun Hee Kim MD (Resident), Sang Hyun Lee MD (Clinical Assistant Professor)

Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul, Korea

Received 7 February 2011; revised 5 January 2012; accepted 5 February 2012

Keywords: Abstract Analgesic consumption; Study Objective: To evaluate whether intraoperative low-dose lidocaine infusion decreases postoperative Gastrectomy; analgesic consumption, ileus, and duration of hospital stay. Hospital length of stay; Design: Prospective, randomized, double-blinded trial. Intravenous lidocaine Setting: Operating room in a university hospital. Patients: 48 ASA physical status 1 and 2 men scheduled for subtotal gastrectomy. Interventions: Patients were randomly allocated to two groups to receive either intravenous (IV) lidocaine 1.5 mg/kg 20 minutes before incision followed by a continuous lidocaine infusion of 1.5 mg/kg/ hr until the end of surgery (lidocaine group) or saline in a similar manner (control group). Measurements: Outcomes such as pain intensity, postoperative analgesic consumption, duration of ileus, and hospital length of stay (LOS) were recorded. Main Results: There were no differences in total consumption of IV patient-controlled analgesia (IVPCA) or pain scores at 24, 48, or 72 hours postoperatively. However, lidocaine group patients had significantly decreased average supplemental pethidine requirement per patient for pain control until 72 hours postoperatively [150 (75-200) mg vs 50 (50-150) mg, P = 0.039] and hospital LOS (9.5 ± 3 d vs 8.7 ± 1 d, P = 0.006, 95% CI: - 0.3 - 1.9 d) than control group patients. However, no differences were noted between the groups in pain intensity or duration of ileus. Conclusions: Intraoperative IV low-dose lidocaine infusion decreased opioid consumption and hospital LOS after gastrectomy. © 2012 Elsevier Inc. All rights reserved.

1. Introduction

Subtotal or total open gastrectomy for gastric malignant ☆ Financial support: departmental funding only. tumor is a common surgery performed in Korea. Reduced ⁎ Correspondence: Myung Hee Kim, MD, PhD, Department of pain intensity, analgesic consumption, and accelerated Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunk- recovery of bowel function are important factors in improving wan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul, Korea 135-710. Tel.: +82 2 3410-2470; fax: +82 2 3410-0361. the postoperative recovery course, with consequent shortened E-mail address: [email protected] (M.H. Kim). hospital length of stay (LOS).

Epidural analgesia is appropriate after gastrectomy. All surgical procedures for subtotal gastrectomy were However, insertion of epidural catheters has potential risks standardized in this hospital and performed by two surgeons and may be declined by patients. Intravenous (IV) opioid is a who were highly experienced in this procedure. Basic popular analgesic after abdominal surgeries [1-3] despite noninvasive blood pressure (BP), HR, electrocardiogram, opioid-related side effects such as nausea and emesis, end-tidal CO2, peripheral pulse oximeter, core body respiratory depression, pruritus, and prolonged ileus. To temperature, and Bispectral Index (BIS) monitors were reduce the adverse systemic effects of opioid analgesics, attached to all patients. Anesthesia was induced with multimodal analgesia has been implemented [1-4]. thiopental sodium 5 mg/kg. Vecuronium 1.0 mg/kg was Lidocaine as a sodium channel blocker has analgesic, given to achieve neuromuscular block and to facilitate antihyperalgesic, and anti-inflammatory effects [5,6]. Peri- tracheal intubation. To maintain controlled ventilation, operative IV lidocaine infusion improves postoperative intermittent doses of vecuronium were given if needed. All outcomes such as pain score, postoperative analgesic patients received sevoflurane with 50% oxygen and air to consumption, anti-inflammatory response, bowel function, maintain anesthesia according to BIS values and hemody- and hospital LOS, particularly after visceral surgery [1-4,7,8]. namic variables within 20% of preoperative values. To However, previous studies of abdominal and urologic surgery ensure similar anesthetic depth in all groups during surgery, showing a benefit have not standardized dose or duration of BIS was maintained between 35 and 45. No supplemental the lidocaine infusion. Postoperative IV lidocaine infusion opioid was given to patients in either group during following intraoperative IV infusion appears to provide maintenance of anesthesia so as to avoid an influence on excellent postoperative recovery and convalescence [1]. sevoflurane consumption and BIS during anesthesia. Peri- Although postoperative lidocaine infusion in previous operative fluid was managed with Ringer's lactate solution at studies was safe and well tolerated, the possible side effects a rate of 8 mL/kg/hr. Neuromuscular block was reversed with [9] of lidocaine during infusion requires continuous clinical pyridostigmine 0.3 mg/kg and glycopyrrolate 0.015 mg/kg. monitoring and, consequently, additional medical cost. There- Postoperative analgesia was started with pethidine 0.5 mg/kg fore, the aim of this study was to determine if low-dose IV given 15 minutes to the end of surgery. lidocaine infusion, restricted until the end of surgery, reduced On arrival at the Postanesthesia Care Unit (PACU), postoperative pain, postoperative analgesic consumption, dura- patients were connected to an IV patient-controlled analgesia tion of ileus, and LOS after open subtotal gastrectomy in men. (IVPCA) system with fentanyl 1,500 μg and ketorolac 180 mg in 100 mL of saline, to deliver a bolus of 15 μgof fentanyl and 1.8 mg of ketorolac with a lockout time of 15 minutes and a basal rate of 15 μg/hr of fentanyl and 1.8 mg/ 2. Materials and methods hr of ketorolac. For postoperative analgesia, IVPCA was provided for a maximum of three days, and supplemental After obtaining Samsung Medical Center Ethics Com- pethidine was given on patient request, with additional mittee approval (IRB File No: 2009-06-043-004) and boluses of 0.25 mg/kg given at 20 to 30-minute intervals on written, informed consent, 48 ASA physical status 1 and 2 the hospital ward. Fentanyl patch also was given in addition men, aged 45-60 years, who were scheduled for elective to the IVPCA and pethidine as needed for pain. subtotal gastrectomy during general anesthesia were The study medication, either lidocaine or saline, was enrolled prospectively in this randomized, double-blinded prepared by an anesthesiologist who was involved in the study. Patients with severe hepatic, renal, cardiac, anesthetic management and who was not blinded to the study respiratory, or endocrine disease; those taking analgesics groups. However, that anesthesiologist did not take part in preoperatively; and those with allergy to local anesthetic further management of patients’ postoperative pain control or were excluded from the study. Patients with severe data collection associated with this study. Opioid consump- hypotension [mean arterial pressure b 60 mmHg] or tion and related side effects, and adverse reactions to bradycardia [heart rate (HR) b 40 beats per minute lidocaine such as lightheadedness, tinnitus, metallic taste, (bpm)], arrhythmia, or urticaria due to lidocaine infusion perioral numbness, drowsiness, and visual disturbances, were during the surgery also were excluded. assessed in the PACU by medical personnel who were Patients were randomized to two groups by a computer- blinded to patients’ study group allocation. Patients, generated code of random numbers to receive either surgeons, and medical investigators who were involved in intraoperative systemic lidocaine infusion (lidocaine data collection during the hospital stay were all blinded to group) or normal saline infusion (control group). For group allocation. patients in the lidocaine group, an IV bolus of lidocaine Consumption of analgesics and any related side effects, 1.5 mg/kg was given approximately 20 minutes before skin and visual analog scores (VAS) on a scale of 0-10 for pain incision, followed by a continuous IV lidocaine 1.5 mg/kg/ intensity (0 = none, 10 = worst pain) at rest were obtained 24, hr infusion until the end of skin closure. Control group 48, and 72 hours postoperatively. To assess restoration of patients received the same amount of bolus and continuous bowel function, patients were asked to report the time to first infusion of saline. passage of gas and first defecation. Intraoperative lidocaine infusion postgastrectomy 467

We chose hospital LOS as the primary study endpoint. sevoflurane(%),BIS,totalfluid amount, total blood loss, and According to a previous study of laparoscopic colectomy [1], pethidine consumption in the PACU were comparable between a sample size of 20 patients per group was sufficient to permit the groups (Table 1). Lidocaine-associated hemodynamic discharge from the hospital approximately one day earlier in changes such as severe hypotension, bradycardia, and the lidocaine group, with a type I error of 0.05 and a power of arrhythmia were not observed in any patient from the lidocaine 80%. Therefore, we enrolled 24 patients in each group. group during the surgery. In addition, no patient complained of Statistical analysis was conducted using SPSS software lidocaine-induced toxicity such as lightheadedness, perioral (version 18.0; SPSS, Inc., Chicago, IL, USA). Comparison numbness, metallic taste, dizziness, and visual disturbances between groups in demographic and perioperative clinical data, during the PACU stay. No patient from either group received IVPCA amount, extra-analgesic consumption, VAS scores opioids during the surgery. Pethidine requirement in the PACU recorded over the postoperative 24, 48, and 72 hours, return of was similar between the groups. bowel function, and hospital LOS were undertaken using the t- Pain intensity on VAS and consumption of IVPCA at 24, test or Mann Whitney U test as appropriate. The number of 48, and 72 hours after the surgery did not differ between the patients who requested extra pain medication and the frequency groups (Table 2). In the comparison of extra-analgesic of opioid-related side effects were analyzed by Chi square test consumption such as pethidine, fentanyl patch, and PCA or Fisher's Exact test. All data are expressed as means ± refill, the number of patients who requested extra pain standard deviation (SD), medians (interquartiles), or numbers medication was comparable between the groups. However, of patients. A P-value b 0.05 was statistically significant. the median (interquartile) amount of pethidine per patient who requested it was significantly lower in the lidocaine group than the control group during the first three days postoperatively [50 (50-150) mg vs 150 (75-200) mg, P = 3. Results 0.039] (Table 3). Considering the return of bowel function after surgery, there were no significant differences between One patient in the control group was excluded from the the groups. Times to first flatus and first defecation were study when his surgical procedure was changed from subtotal to comparable between the groups. However, there was a total gastrectomy (Fig. 1). Thus, 23 control group patients and significant difference in LOS between the two groups. The 24 lidocaine group patients completed the study. Patients’ lidocaine group was discharged home significantly earlier characteristics, ASA physical status, surgical duration, end-tidal than control group patients (9.5 ± 3 d vs 8.7 ± 1 d, P =0.006;

Enrollment Assessed for eligibility (n = 48 )

Randomized (n = 48 )

Allocation Allocated to control group (n = 24 ) Allocated to lidocaine group (n = 24 )

Follow-Up Lost to follow-up due to changed surgical procedure (n = 1) Lost to follow-up (n = 0 )

Analysis

Analyzed (n = 24 ) Analyzed (n = 23)

Fig. 1 The Consolidated Standards of Reporting Trials (CONSORT) Flow Diagram. 468 J.G. Kang et al.

Table 1 Demographic and clinical data of patients undergoing Table 3 Supplemental analgesics during the first three days open gastrectomy after surgery Control group Lidocaine P-value Control Lidocaine P-value (n=23) group (n=24) group (n=23) group (n=24) Age (yrs) 56.4 ± 7 55.2 ± 8 0.553 Pethidine chloride Weight (kg) 67.3 ± 7 72.0 ± 25 0.151 requested patients (n) 15 17 0.039 Height (cm) 167.3 ± 5 167.5 ± 6 0.353 amount/patient (mg) 150 (75-200) 50 (50-150) A/E (n) 5/18 6/18 Fentanyl patch (n) 3 1 ASA physical 14/ 9 16/8 IVPCA refill (n) 2 1 status (1/2) Data are medians (interquartile ranges) or numbers of patients. Duration of surgery 192.4 ± 31 175.8 ± 26 0.505 IVPCA=intravenous patient-controlled analgesia. (min) End-tidal sevoflurane 1.9 ± 0.3 1.8 ± 0.3 0.71 (%) for malignant gastric tumors in men aged 45 to 60 years. In BIS values during 40.2 ± 4 38.9 ± 3 0.95 contrast to previous studies [2,7], we were unable to show a surgery statistically significant quality of pain control or duration of Total fluid during 1889 ± 347 1883 ± 382 0.490 ileus with such a low-dose systemic lidocaine infusion. surgery (mL) Total bleeding during 175 ± 64 171 ± 62 0.815 Controlled pain management and reduced requirement of surgery (mL) analgesics provide good patient satisfaction and improve Pethidine in PACU 55.2 ± 24 49.0 ± 24 0.413 outcomes after extensive surgery such as gastrectomy. (mg) Although opioids are the most commonly used analgesic, Data are means ± SD or numbers of patients. they have detrimental side effects that may lead to prolonged A/E=advanced/early cancer, BIS=bispectral index score, PACU=Post- LOS. Because of the therapeutic effects of lidocaine as a anesthesia Care Unit. sodium channel blocker, perioperative systemic lidocaine infusion recently was suggested as a useful anesthetic adjunct with improved postoperative outcomes, especially after visceral 95% CI: - 0.3 - 1.9 d) (Table 4). There were two episodes of surgery [1-4,7,8]. Although there was no benefitinpain minor wound healing disturbances, which delayed discharge outcome during the 72 hours after surgery in the lidocaine- from the hospital, in two control group patients. Otherwise, treated patients, supplemental pethidine requests per patient delayed discharge due to any surgical complication was not other than IVPCA during the postoperative 72 hours were found in either study group. significantly fewer in the lidocaine group at similar pain ratings. Less analgesic consumption in our lidocaine group may be explained by a previous study that suggested that a small dose 4. Discussion of lidocaine prevented the induction of central hyperalgesia and reduced postoperative analgesic consumption [10]. Intraoperative low-dose lidocaine infusion 1.5 mg/kg/hr However, the true benefits, such as pain relief, opioid following a bolus injection of lidocaine 1.5 mg/kg sparing, restoration of bowel function, and earlier hospital significantly decreased postoperative opioid consumption discharge [1-4,7,8] remain uncertain owing to variations in and LOS by an average 0.8 days after subtotal gastrectomy surgery type, study period after surgery, and the amount and duration of the lidocaine infusion. Previous studies of visceral surgery [1-4,7,8] examined postoperative outcomes with Table 2 Consumption of intravenous patient-controlled systemic lidocaine infusion from one to 24 hours after analgesia (IVPCA) and visual analog scores (VAS) over the first 72 hours after surgery intraoperative infusion. Perioperative lidocaine infusion Control Lidocaine P-value group (n=23) group (n=24) Table 4 Recovery of bowel function and hospital length of stay (LOS) Postoperative 24 hours total IVPCA (mL) 45 (40-45) 40 (40-45) 0.84 Control Lidocaine P-value VAS 5 (4-7) 4 (4-7.5) 0.92 group (n=23) group (n=24) (95% CI) Postoperative 48 hours First flatus (hrs) 94.3 ± 26 92.7 ± 19 0.245 total IVPCA (mL) 40 (30-40) 35 (30-40) 0.49 First defecation (hrs) 125.1 ± 41 115.5 ± 21 0.141 VAS 5 (4-6.5) 5 (3.5-5) 0.68 Hospital LOS (d) 9.5 ± 3 8.7 ± 1 0.006 Postoperative 72 hours (-0.3 - 1.9) total IVPCA (mL) 15 (10-22.5) 20 (10-25) 0.26 Data are means ± SD. VAS 5 (4-6.5) 4 (3-4.5) 0.35 95% CI = 95% confidence interval for mean difference between the two Data are medians (interquartile ranges). groups. Intraoperative lidocaine infusion postgastrectomy 469 provided better pain relief after radical prostatectomy [7], addition, our study candidates were restricted to men in a laparoscopic colectomy [1], and colonic surgery [4],whereas narrow age range of 45 and 60 years, undergoing subtotal in a study by Herroder et al [8] and Koppert et al [2],lidocaine gastrectomy to avoid the possible confounding effects of infusion until 4 hours after the end of colorectal surgery and gender, age, and extent of surgery on the study parameters. until one hour after the end of major abdominal surgery did Therefore, we suggest that the impact of intraoperative low- not show a preventive effect on postoperative pain intensity. lose lidocaine infusion on hospital LOS was of true benefit, Nevertheless, a lidocaine infusion of longer duration appears consistent with previous results [1,7,8]. Interestingly, to provide the most significant impact on postoperative according to previous studies, earlier discharge in the morbidity and hospital LOS. In a study by Kaba et al [1],the lidocaine group was suggested to be related to the rapid authors suggested that the prolonged infusion of lidocaine for resolution of postoperative ileus [1,7,13]. Because lidocaine 24 hours following intraoperative infusion presented signif- has anti-inflammatory effects, early recovery from ileus after icantly improved outcomes for all study parameters such as surgery may be attributed to the administration of lidocaine. pain scores, opioid consumption, subjective feeling of fatigue, Contrary to our expectations, shortened hospital LOS in return of bowel function, and hospital LOS after laparoscopic the lidocaine group did not significantly affect restoration of colectomy. Tremont-Lukas et al [11] also reported that the bowel function in this study. Although the time to first higher dose of lidocaine, 5 mg/kg, was more effective in defecation was earlier by 10 hours in the lidocaine-treated alleviating neuropathic pain than was a lower infusion, which patients, the times to first passage of flatus and defecation as did not differ from placebo for relief of pain. Lidocaine restoration of bowel function were not statistically different infusion with a varied dose and duration in previous studies between groups in this study. Lidocaine-induced modulation [1-4,7,8] has been suggested as safe and without serious side of the surgical stress response also has been suggested as a effects; however, perioral numbness and tinnitus were reason for the shortened LOS [8]. In the assessment of reported in one study with IV lidocaine pain management peripheral white blood cell (WBC) subsets as inflammatory [9]. Therefore, medical observation may be required as long as response during the 5 postoperative days in this study, the lidocaine infusion is continued. intraoperative lidocaine infusion showed a trend toward Recently, with respect to the reduction of medical attenuation of surgery-induced increases in total WBC and expenses of patients and efficient use of hospital resources, neutrophil count and a decrease in lymphocytes, although hospital LOS after surgery seems to be a particularly those results were statistically insignificant (data not shown). important outcome in Korea. This is especially relevant in Hence, further study is needed to clearly document the major surgery such as gastrectomy, since it is one of the most reason for the shortened hospital LOS with lidocaine prevalent surgical procedures in Korea. We found that infusion that was seen in this study. duration of hospital stay was significantly shorter in the The limitations of this study are as follows. First, pain lidocaine group than the control group (8.7 vs 9.5 d) intensity on movement was not assessed. Pain scores at rest following gastrectomy in this study. Previous studies using did not differ significantly between groups; however, pain on larger doses and longer duration of perioperative lidocaine movement, if assessed, might have shown significant results. infusion in radical retropubic prostatectomy [7], colorectal Second, we followed the previous study [1] as a reference in surgery [8], and laparoscopic colectomy [1], compared with performing the power analysis, including 48 participants in this study, showed an earlier hospital discharge by this study. The key finding of a 0.8 day reduction in hospital approximately one day. However, a recent study by Bryson LOS with lidocaine may not have enough power for a Type 1 et al [12] in Canada showed that an intraoperative lidocaine error = 0.05 or Type II error = 0.8 in 48 patients in this study. infusion of 3 mg/kg/hr after a bolus of 1.5 mg/kg did not More patients in each group might have been needed to have reduce hospital LOS following abdominal hysterectomy. In a sufficient power. study by Bryson et al, the wide variability in hospital LOS In conclusion, a small dose of systemic lidocaine infusion after abdominal hysterectomy from day 1 through day 4 in limited to the intraoperative period may have a beneficial both control group and lidocaine-treated patients was due to effect regarding reduced opioid consumption and hospital social reasons, such as a patient's preference to stay longer LOS in men receiving subtotal gastrectomy. and wait for staple removal [12]. In contrast, the LOS in our study was decided by the surgeon without delaying the real discharge time when patients met the standardized discharge protocol, such as return to a light diet without nausea and References vomiting, no signs of wound healing disturbances, absence of infectious parameters in blood chemistry, and restored [1] Kaba A, Laurent SR, Detroz BJ, et al. Intravenous lidocaine infusion bowel movement. Despite the marginal decrease in hospital facilitates acute rehabilitation after laparoscopic colectomy. Anesthe- LOS in the lidocaine-treated group, our study result may be siology 2007;106:11-8. [2] Koppert W, Weigand M, Neumann F, et al. Perioperative intravenous meaningful in that patient discharge was determined lidocaine has preventive effects on postoperative pain and morphine according to the discharge protocol by the surgeons, all of consumption after major abdominal surgery. Anesth Analg 2004;98: whom were blinded to the patient group allocation. In 1050-5. 470 J.G. Kang et al.

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