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Is perioperative administration of 5% dextrose effective in reducing the incidence of PONV in laparoscopic cholecystectomy?: A randomized control trial
Journal of Clinical Anesthesia 40 (2017) 7–10
Contents lists available at ScienceDirect
Journal of Clinical Anesthesia
Original Contribution
Is perioperative administration of 5% dextrose effective in reducing the incidence of PONV in laparoscopic cholecystectomy?: A randomized control trial Ankita Mishra a, Ravinder Kumar Pandey a,⁎, Ankur Sharma a, Vanlalnghaka Darlong a, Jyotsna Punj a, Devalina Goswami a, Renu Sinha a, Vimi Rewari a, Chandralekha Chandralekha a, Virinder Kumar Bansal b a b
Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India Department of Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India
a r t i c l e
i n f o
Article history: Received 9 July 2016 Received in revised form 23 March 2017 Accepted 31 March 2017 Available online xxxx Keywords: Anesthesia Postoperative nausea and vomiting Laparoscopic cholecystectomy Apfel score
a b s t r a c t Study objective: To compare the incidence of postoperative nausea and vomiting (PONV) during perioperative administration of 5% dextrose and normal saline in laparoscopic cholecystectomy. Design: Prospective, randomized, double-blind trial. Setting: Operating rooms in a tertiary care hospital of Northern India. Patients: One hundred patients with American Society of Anesthesiologists status I to II undergoing laparoscopic cholecystectomy were enrolled in this study. Interventions: Patients were randomized into two groups [normal saline (NS) group and 5% dextrose (D) group]. Both the groups received Ringer acetate (Sterofundin ISO) intravenously as a maintenance fluid during intraoperative period. Besides this, patients of group NS received 250 ml of 0.9% normal saline and patients of group D received 5% dextrose @ 100 ml/h started at the time when gall bladder was taken out. It was continued in the postoperative period with the same rate till it gets finished. Measurements: Incidence of PONV, Apfel score, intraoperative opioids used and consumption of rescue antiemetics. Main results: Demographic data was statistically similar. Out of total 100 patients, 47 patients (47%) had PONV. In group D, 14 patients (28%) had PONV while in group NS, 33 patients (66%) had PONV within 24 h of surgery (p value 0.001). The incidence of PONV was reduced by 38% in group D which is significantly lower when compared with that of group NS (p value 0.001). The consumption of single dose of rescue antiemetics in group D was also reduced by 26% when compared to that of group NS (p value 0.002). Conclusions: Perioperative administration of 5% dextrose in patients undergoing laparoscopic surgery can reduce PONV significantly and even if PONV occurs, the quantity of rescue antiemetics to combat PONV is also reduced significantly. © 2017 Elsevier Inc. All rights reserved.
1. Introduction Postoperative nausea vomiting (PONV) and pain are two major concerns for patients undergoing surgery. In spite of multiple advances to reduce these, patients continue to rank nausea and vomiting as the most undesirable adverse effect of surgical procedure [1,2,3,4]. With the availability of modern anesthetic techniques and better antiemetic drugs, the overall incidence of PONV has lowered down to around 30%, which is still a significant number [5]. The scenario is worse for ⁎ Corresponding author at: Department of Anaesthesiology, Pain Medicine and Critical Care Room no. 5013, 5th floor Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. E-mail address: [email protected] (R.K. Pandey).
http://dx.doi.org/10.1016/j.jclinane.2017.03.048 0952-8180/© 2017 Elsevier Inc. All rights reserved.
high-risk patients, where the incidence of PONV is as high as 80% [6]. It is estimated that a single episode of vomiting increases stay in post anesthesia care unit (PACU) by about 25 min and patients usually rate PONV to be more problematic than postoperative pain [7,8]. It is one of the leading causes of unexpected admission to the hospital following daycare surgery [9]. Risk factors for PONV consist of females, nonsmokers, postoperative use of opioids and previous history of PONV or motion sickness. These factors have been incorporated in the simplified PONV-risk score, the “Apfel-score”. It includes all these 4 variables and assigns one point for each [10]. There is unnecessary rise in costs if numbers of patients need to be treated to prevent one patient from PONV are more. This cost of prophylactic treatment may be reduced by keeping number of patients to be treated small and by usage of multimodal approaches [10]. Many
8
A. Mishra et al. / Journal of Clinical Anesthesia 40 (2017) 7–10
studies in the past have proved that preoperative intravenous fluid therapy decreases postoperative nausea and vomiting presumably by reducing hypovolemia [11,12,13]. Other studies have proved that giving oral carbohydrate load preoperatively was associated with reduced incidence of PONV presumably by lowering down the postoperative catabolism and insulin resistance [14,15]. In the present study, we observed the relationship between perioperative intravenous dextrose administration and the incidence of PONV in patients undergoing laparoscopic cholecystectomy and its effect on patient having high (3,4) and low (0,1,2) Afpel score. 2. Material and methods The study was approved by the Institutional Ethics Committee and was registered with the Clinical Trials Registry of India (CTRI number: CTRI/2016/03/006697). One hundred American Society of Anesthesiologists (ASA) status I to II adults, aged 18–65 years scheduled for laparoscopic cholecystectomy were included in this prospective, randomized, double-blind trial at a tertiary care hospital in Northern India (Fig. 1). An informed written consent was obtained from all the patients prior to the initiation of the study. Patients with these conditions were excluded from the study i.e. patient refusal, history of coronary artery disease/ congestive heart failure, diabetes mellitus, renal insufficiency, hypertension, gastro esophageal reflux disease/peptic ulcer disease, receiving antiemetics/steroids, pregnant females, abnormal blood glucose on the morning of surgery (fasting N 140 mg/dl), requiring large volume of intravascular fluid treatment for severe intraoperative hypotension, increased intracranial tension due to some pathology e.g. intracranial space occupying lesion (ICSOL), meningitis, pseudotumorcerebri etc., cancer patients on chemotherapy and opioids, vestibular dysfunction of Meniere's Disease. Patients were randomized into two groups (50 patients in each group) normal saline (NS) group and 5% dextrose (D) group with the help of computer generated random number table. Sealed opaque envelopes were opened in the OT and study fluid (normal saline or 5% dextrose) was decided according to the particular randomized group. All the 100 patients received the allocated intervention according to their groups allotted. The Sample size was selected on the basis of previous studies where b50 patients in each group were taken.
A thorough pre-anesthetic work up was carried out for all the patients. General anesthesia was induced in all patients with intravenous (IV) propofol, fentanyl and atracurium. Maintenance of anesthesia was done with isoflurane in oxygen and air (50:50). Intra-operatively, IV fentanyl (0.5 mcg/kg) was administered if heart rate (HR) and blood pressure (BP) is N20% of the base line excluding the other causes of increase in HR and BP like raised end tidal carbon dioxide (EtCO2) and due dose of nondepolarizing muscle relaxant. All patients received IV dexamethasone (4 mg) after induction. During intra operative period both the groups received ringer acetate solution (Sterofundin ISO) intravenously @ 100 ml/h as maintenance fluid. Apart from this, patients of group NS received 250 ml of 0.9% normal saline and patients of group D received 5% dextrose @ 100 ml/h started at the time when gall bladder was taken out. It was continued in the postoperative period with the same rate till it gets finished. For the purpose of blinding, the label of the study fluid (5% dextrose or normal saline) was removed by a senior anesthesiologist to prevent observer's bias. The person who was administering the study fluid was kept unaware about the type of study fluid. In the recovery room or in the ward, an independent observer who was not aware of the type of study fluid, noted the numbers of PONV episodes. Parameters like HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), SpO2 (% saturation of hemoglobin), EtCO2, airway pressure (Paw) were noted at time of induction, intubation, after 10 min and then at the difference of 10 min till extubation. All patients received injection paracetamol (15 mg/kg) intravenously at the end of surgery and neuromuscular blockade was reversed with injection neostigmine and glycopyrrolate. All patients were assessed for PONV by using visual analogue scale (VAS) from 0 to 10, where 0 means no nausea and 10 means worst possible nausea or any episode of retching or vomiting. Patients with VAS score of 3 or more received ondansetron 4 mg intravenously as a first line antiemetic treatment. However, if PONV persisted after 30 min after above treatment, then metoclopramide 10 mg was administered intravenously. The VAS score for PONV was recorded after 30 min, 60 min, 90 min, 6 h, and 24 h after patient arrival in PACU. The total amount of rescue antiemetic (intravenous ondansetron in an incremental dose of 4 mg) in 24 h postoperatively was noted for every patient.
Fig. 1. Consort diagram.
A. Mishra et al. / Journal of Clinical Anesthesia 40 (2017) 7–10
Patients were kept in PACU for 6 h after the surgery. After this period patients were shifted to ward and kept there up to 24 h following surgery. The primary outcome of this study was to observe the incidence of PONV in both the groups. The secondary outcome of the study was to find out the consumption of rescue antiemetics, Apfel score, intraoperative opioids and fluids administered in both the groups. 3. Statistical analysis Data analysis was carried out using Stata 12.0 (College station, Texas, USA). The data was presented as number (%) and mean ± standard deviation (SD) as appropriate. The baseline categorical and continuous characteristics were analyzed between the groups using Chi square test/Fisher's exact test and Student's ‘t’ test for independent samples respectively. The primary outcome, incidence of PONV were compared between the two groups using ‘Z’ test and ANCOVA (Analysis of covariance) was carried out to adjust for the imbalance found in total intraoperative opioid consumption between the two groups. The results were presented as both unadjusted and adjusted difference in the incidence of PONV and 95% confidence interval. The change in hemodynamic parameters over a period of time between the two groups was assessed using repeated measures ANOVA (Analysis of variance). The p b 0.05 was considered statistically significant. 4. Results There was no significant intergroup difference in the base line characteristics like age, gender, height, weight, ASA status, total duration of surgery/anesthesia, and intraoperative fluid administered (Table 1). The mean body mass index (BMI) of the patients in group NS was 24.37 ± 3.62 kg/m2 while in group D 22.88 ± 2.84 kg/m2. This difference was statistically significant but clinically within the normal range of BMI. The distributions of patients according to smoking status were comparable in both groups. The distribution of patients according to Apfel score was also comparable in both the groups (p value 0.616). In group NS all the patients had low Apfel score while in group D 49 patients had low Apfel score and only one patient had high Apfel score. The mean of total intraoperative opioids used in group NS versus group D were comparable at all time points after adjusting. Adjustment was done using RM ANCOVA (Repeated Measures Analysis of covariance) test (Table 1). Table 1 Demographic characteristics, Apfel score, duration of anesthesia/surgery and total intraoperative opioids and fluids used in both groups. Characteristics
Group NS Mean ± SD
Group D Mean ± SD
p Value
Age (years) Weight (kilograms) Height (centimeters) BMI (kg/m2) Nonsmokers Smokers ASA 1 ASA 2 Male Female Apfel score 0 Apfel score 1 Apfel score 2 Apfel score 3 Apfel score 4 Anesthesia time (minutes) Surgical time (minutes) Total intraoperative opioids (micrograms) Total intraoperative fluids (milliliter)
39.6 ± 11.54 62.22 ± 9.86 159.8 ± 8.40 24.37 ± 3.62 40 (80%) 10 (20%) 40 (80%) 10 (20%) 17 (34%) 33 (66%) 7 (14%) 39 (78%) 4 (8%) 0 (0%) 0 (0%) 67.1 ± 17.41 40 ± 13.28 148.8 ± 33.02
37.42 ± 12.00 57.68 ± 10.03 158.5 ± 10.30 22.88 ± 2.84 42 (84%) 8 (16%) 41 (82%) 9 (18%) 11 (22%) 39 (78%) 6 (12%) 41 (82%) 2 (4%) 1 (2%) 0 (0%) 65.2 ± 14.39 38.7 ± 10.82 134.5 ± 34.14
0.357 0.02⁎ 0.49 0.02⁎ 0.603
0.55 0.59 0.03⁎
611 ± 136.38
605 ± 138.96
0.82
⁎ p b 0.05.
0.799 0.181 0.616
9
Table 2 Overall incidence of PONV in both the groups. PONV
Group NS
Group D
p Value
Absent Present Unadjusted difference (95% confidence interval) Adjusted difference (95% confidence interval)
17 (34%) 33 (66%) 38.5 (19.9–56.0)
36 (72%) 14 (28%)
0.001⁎
38.49 (19.47–57.51)
Adjusted for total intraoperative opioids. ⁎ p b 0.05.
Out of total 100 patients, 47 patients (47%) had PONV (Table 2). In group D, 14 patients (28%) had PONV within 24 h of surgery while in group NS, 33 patients (66%) had PONV with a significant p value (p value 0.001). None of the patients had any PONV within first 30 min. Twenty out of 100 patients had PONV score ≥ 3 in first 60 min for which they were given rescue antiemetics. Twenty seven patients had PONV during first 90 min, 16 patients after 120 min and 9 patients after 6 h of surgery. Only 1 patient had PONV after 24 h of surgery (Table 3). Out of the total 14 patients of group D who had PONV, only 3 (6%) patients had to be given 1 repeated doses of ondansetron 4 mg while 11 (22%) patients received only single dose of ondansetron 4 mg to combat PONV. In the NS group 33 (66%) out of 50 patients received rescue antiemetics. In this group 24 patients (48%) received only one dose of ondansetron 4 mg, 7 patients (14%) received one repeated dose of ondansetron while 2 patients (4%) received ondansetron 4 mg + metoclopramide 10 mg. There was only one patient with high Apfel Score while the rest of 99 patients had low Apfel score. Due to this highly uneven distribution in Apfel scoring, analysis could not be done. 5. Discussion The present study is unique in a way that it demonstrates a 38% reduction in PONV in patients receiving perioperative dextrose when compared to patients receiving perioperative normal saline which is the primary outcome of the study. This reduction is even more than that of previous studies. The only difference between the groups was 250 ml of 5% dextrose infusion at the rate of 100 ml/h in group D patients. The secondary outcome of the study which is to find out the consumption of rescue antiemetics in both the groups has also shown better results in the group receiving dextrose. There is 26% reduction in use of single dose of ondansetron 4 mg in dextrose group. None of the patients received metoclopramide injection in dextrose group. In light of its ease, low risk, and benefit to patient care and satisfaction, this therapeutic modality could be considered. Postoperative nausea vomiting is one of the limiting factors in early discharge of daycare surgery patients and is a leading cause of unanticipated hospital admission. Current approaches to prevent and treat PONV are limited and N25% of patients experience PONV within 24 h postoperatively [5]. In fact, PONV can be as frequent as 80% among high-risk patients [6]. Despite this, universal pharmacologic PONV prophylaxis does not seem to be cost effective, and is associated with increased side effects. Adverse effects of these drugs are headache, lightheadedness, dizziness, and constipation (serotonin antagonists) and sedation, lethargy, agitation, extrapyramidal effects, prolonged QT interval (dopamine antagonists). Although some advocate prophylactic antiemetic therapy for high-risk patients, with rescue antiemetic treatment for episodes of PONV, the optimal approach remains still unclear. There are some adjuvant therapies which decrease the incidence of PONV. Various studies identified dehydration as an important factor in the incidence of PONV [16,17]. Lambert K G et al. noted that preoperative fluid bolus using 4-2-1 rule decreases the incidence of PONV significantly [18]. The present study demonstrates a novel and comparatively cheaper method to reduce the incidence of PONV by giving 5% dextrose perioperatively in nondiabetic adult patients undergoing laparoscopic
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A. Mishra et al. / Journal of Clinical Anesthesia 40 (2017) 7–10
Table 3 Patients with PONV in both groups within 24 h of surgery at different time points. Time
30 min 60 min 90 min 120 min 6h 24 h
Group NS No. of patients with PONV N = 50
Group D No. of patients with PONV N = 50
Total No. of patients with PONV N = 100
0 14 17 10 7 1
0 6 10 6 2 0
0 20 27 16 9 1
cholecystectomy. There are some recent studies on preoperative administration of carbohydrate rich drinks and comparison of PONV with fasting patients. Yilmaz N et al. showed that PONV and antiemetic consumption was lower in group with preoperative oral carbohydrate compared to group fasting (p = 0.001) [19]. This result is in contrary to that in 200 women patients in a study by Lauwick SM et al. scheduled for thyroidectomy [20]. This study is supported by another study by Dabu-Bondoc S et al. in which 62 nondiabetic, ASA class I or II nonsmoking outpatients scheduled for gynecologic laparoscopic and hysteroscopic procedures were taken. They concluded that post anesthesia IV dextrose administration resulted in improved PONV management as defined by reductions in antiemetic rescue medication requirements and PACU length of stay [21]. However, results of a similar study done by Patel P et al. on 162 ASA I and II female patients showed that the administration of dextrose during emergence from anesthesia was not associated with a difference in the incidence or the severity of PONV in the first 2 h after anesthesia [22]. Reduced incidence of PONV in dextrose group might be because of caloric supplementation in this group which lowered down postoperative catabolism and insulin resistance and improved patient comfort and thus risk of postoperative nausea and vomiting. It also has some direct local action on the wall of gastrointestinal tract which increases the osmotic pressure and thus reduces muscle contraction. The limitations of the present study are: it was carried out in a single centre in Indian population. Extrapolation of results to the other populations should be guarded. The number of patients in high Apfel group were very less, so the risk association with high and low Apfel score could not be done. Other outcomes like postoperative pain and post discharge nausea and vomiting were not studied. The population taken up for this study is adult population so the results cannot be extrapolated to paediatric age group. 6. Conclusion Perioperative administration of 5% dextrose at 100 ml/h can reduce the incidence of PONV and decrease the consumption of rescue antiemetics in patients 24 h following laparoscopic surgery.
Conflicts of interest None. References [1] Chandrakantan A, Glass PS. Multimodal therapies for postoperative nausea and vomiting, and pain. Br J Anaesth 2011;107(S1):127–40. [2] Smith HS, Smith EJ, Smith BR. Post operative nausea and vomiting. Ann Palliat Med 2012;1(2):94–102. [3] Janicki PK, Vealey R, Liu J, Escajeda J, Postula M, Welker K. Genome wide association study using pooled DNA to identify candidate markers mediating susceptibility to post operative nausea and vomiting. Anesthesia 2011;115:54–64. [4] Bonica J, Crepps W, Monk B, Bennett B. Post anesthetic nausea, retching and vomiting. Anaesthesia 1958;19:532–40. [5] Cohen MM, Duncan PG, DeBoer DP, Tweed WA. The postoperative interview: assessing risk factors for nausea and vomiting. Anaesth Analg 1994;78:7–16. [6] Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev 2006;3:CD004125. [7] Habib AS, Chen YT, Taguchi A, Hu XH, Gan TJ. Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis. Curr Med Res Opin 2006;22(6):1093–9. [8] Koivuranta M, Laara E, Snare L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia 1997;52:443–9. [9] Wetchler BV. Postoperative nausea and vomiting in day care surgery. Br J Anaesth 1992;69:335–95. [10] Apfel CC, Kranke P, Eberhart LH, Roos A, Roewer N. Comparison of predictive models of post operative nausea and vomiting. Br J Anaesth 2002;88(2):234–40. [11] Maharaj CH, Kallam SR, Malik A, Hassett P, Grady D, Laffey JG. Postoperative intravenous fluid therapy decreases postoperative nausea and pain in high risk patients. Anesth Analg 2005;100:675–82. [12] Apfel CC, Meyer A, Orhan-SungurM Jalota L, Whelan RP, Jukar-Rao S. Supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review. Br J Anaesth 2012;108(6):893–902. [13] Ali SZ, Taguchi A, Holtmann B, Kurz A. Effect of supplemental preoperative fluid on postoperative nausea and vomiting. Anaesthesia 2003;58:780–4. [14] Hausel J, Nygren J, Thorell A, Lagerkranser M, Ljungqvist O. Randomised clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy. Br J Surg 2005;92:415–21. [15] Griffenhagen GB, Hawkins LL. Facts and comparisons: handbook of non prescription drugs. 6th ed. Washington DC: American Pharmacists Association; 1989 107. [16] Nelson TP. Postoperative nausea and vomiting: understanding the enigma. J Perianesth Nurs 2002;17(3):178–87. [17] Hagemann E, Halvorsen A, Holgersen O, Tveit T, Raeder JC. Intramuscular ephedrine reduces emesis during the first three hours after abdominal hysterectomy. Acta Anaesthesiol Scand 2000;44(1):107–11. [18] Lambert KG, Wakim JH, Lambert NE. Preoperative fluid bolus and reduction of postoperative nausea and vomiting in patients undergoing laparoscopic gynecologic surgery. AANA J 2009;77(2):110–4. [19] Yilmaz N, Çekmen N, Bilgin F, Erten E, Ozhan MÖ, Coşar A. Preoperative carbohydrate nutrition reduces postoperative nausea and vomiting compared to preoperative fasting. J Res Med Sci 2013;18(10):827–32. [20] Lauwick SM, Kaba A, Maweja S, Hamoir EE, Joris JL. Effects of oral preoperative carbohydrate on early postoperative outcome after thyroidectomy. Acta Anaesthesiol Belg 2009;60(2):67–73. [21] Dabu-Bondoc S, Vadivelu N, Shimono C, English A, Kosarussavadi B, Dai F, et al. Intravenous dextrose administration reduces postoperative antiemetic rescue treatment requirements and postanesthesia care unit length of stay. Anesth Analg 2013; 117(3):591–6. [22] Patel P, Meineke MN, Rasmussen T, Anderson DL, Brown J, Siddighi S, et al. The relationship of intravenous dextrose administration during emergence from anaesthesia to postoperative nausea and vomiting: a randomized controlled trial. Anesth Analg 2013;117(1):34–42.
Contents lists available at ScienceDirect
Journal of Clinical Anesthesia
Original Contribution
Is perioperative administration of 5% dextrose effective in reducing the incidence of PONV in laparoscopic cholecystectomy?: A randomized control trial Ankita Mishra a, Ravinder Kumar Pandey a,⁎, Ankur Sharma a, Vanlalnghaka Darlong a, Jyotsna Punj a, Devalina Goswami a, Renu Sinha a, Vimi Rewari a, Chandralekha Chandralekha a, Virinder Kumar Bansal b a b
Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India Department of Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India
a r t i c l e
i n f o
Article history: Received 9 July 2016 Received in revised form 23 March 2017 Accepted 31 March 2017 Available online xxxx Keywords: Anesthesia Postoperative nausea and vomiting Laparoscopic cholecystectomy Apfel score
a b s t r a c t Study objective: To compare the incidence of postoperative nausea and vomiting (PONV) during perioperative administration of 5% dextrose and normal saline in laparoscopic cholecystectomy. Design: Prospective, randomized, double-blind trial. Setting: Operating rooms in a tertiary care hospital of Northern India. Patients: One hundred patients with American Society of Anesthesiologists status I to II undergoing laparoscopic cholecystectomy were enrolled in this study. Interventions: Patients were randomized into two groups [normal saline (NS) group and 5% dextrose (D) group]. Both the groups received Ringer acetate (Sterofundin ISO) intravenously as a maintenance fluid during intraoperative period. Besides this, patients of group NS received 250 ml of 0.9% normal saline and patients of group D received 5% dextrose @ 100 ml/h started at the time when gall bladder was taken out. It was continued in the postoperative period with the same rate till it gets finished. Measurements: Incidence of PONV, Apfel score, intraoperative opioids used and consumption of rescue antiemetics. Main results: Demographic data was statistically similar. Out of total 100 patients, 47 patients (47%) had PONV. In group D, 14 patients (28%) had PONV while in group NS, 33 patients (66%) had PONV within 24 h of surgery (p value 0.001). The incidence of PONV was reduced by 38% in group D which is significantly lower when compared with that of group NS (p value 0.001). The consumption of single dose of rescue antiemetics in group D was also reduced by 26% when compared to that of group NS (p value 0.002). Conclusions: Perioperative administration of 5% dextrose in patients undergoing laparoscopic surgery can reduce PONV significantly and even if PONV occurs, the quantity of rescue antiemetics to combat PONV is also reduced significantly. © 2017 Elsevier Inc. All rights reserved.
1. Introduction Postoperative nausea vomiting (PONV) and pain are two major concerns for patients undergoing surgery. In spite of multiple advances to reduce these, patients continue to rank nausea and vomiting as the most undesirable adverse effect of surgical procedure [1,2,3,4]. With the availability of modern anesthetic techniques and better antiemetic drugs, the overall incidence of PONV has lowered down to around 30%, which is still a significant number [5]. The scenario is worse for ⁎ Corresponding author at: Department of Anaesthesiology, Pain Medicine and Critical Care Room no. 5013, 5th floor Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. E-mail address: [email protected] (R.K. Pandey).
http://dx.doi.org/10.1016/j.jclinane.2017.03.048 0952-8180/© 2017 Elsevier Inc. All rights reserved.
high-risk patients, where the incidence of PONV is as high as 80% [6]. It is estimated that a single episode of vomiting increases stay in post anesthesia care unit (PACU) by about 25 min and patients usually rate PONV to be more problematic than postoperative pain [7,8]. It is one of the leading causes of unexpected admission to the hospital following daycare surgery [9]. Risk factors for PONV consist of females, nonsmokers, postoperative use of opioids and previous history of PONV or motion sickness. These factors have been incorporated in the simplified PONV-risk score, the “Apfel-score”. It includes all these 4 variables and assigns one point for each [10]. There is unnecessary rise in costs if numbers of patients need to be treated to prevent one patient from PONV are more. This cost of prophylactic treatment may be reduced by keeping number of patients to be treated small and by usage of multimodal approaches [10]. Many
8
A. Mishra et al. / Journal of Clinical Anesthesia 40 (2017) 7–10
studies in the past have proved that preoperative intravenous fluid therapy decreases postoperative nausea and vomiting presumably by reducing hypovolemia [11,12,13]. Other studies have proved that giving oral carbohydrate load preoperatively was associated with reduced incidence of PONV presumably by lowering down the postoperative catabolism and insulin resistance [14,15]. In the present study, we observed the relationship between perioperative intravenous dextrose administration and the incidence of PONV in patients undergoing laparoscopic cholecystectomy and its effect on patient having high (3,4) and low (0,1,2) Afpel score. 2. Material and methods The study was approved by the Institutional Ethics Committee and was registered with the Clinical Trials Registry of India (CTRI number: CTRI/2016/03/006697). One hundred American Society of Anesthesiologists (ASA) status I to II adults, aged 18–65 years scheduled for laparoscopic cholecystectomy were included in this prospective, randomized, double-blind trial at a tertiary care hospital in Northern India (Fig. 1). An informed written consent was obtained from all the patients prior to the initiation of the study. Patients with these conditions were excluded from the study i.e. patient refusal, history of coronary artery disease/ congestive heart failure, diabetes mellitus, renal insufficiency, hypertension, gastro esophageal reflux disease/peptic ulcer disease, receiving antiemetics/steroids, pregnant females, abnormal blood glucose on the morning of surgery (fasting N 140 mg/dl), requiring large volume of intravascular fluid treatment for severe intraoperative hypotension, increased intracranial tension due to some pathology e.g. intracranial space occupying lesion (ICSOL), meningitis, pseudotumorcerebri etc., cancer patients on chemotherapy and opioids, vestibular dysfunction of Meniere's Disease. Patients were randomized into two groups (50 patients in each group) normal saline (NS) group and 5% dextrose (D) group with the help of computer generated random number table. Sealed opaque envelopes were opened in the OT and study fluid (normal saline or 5% dextrose) was decided according to the particular randomized group. All the 100 patients received the allocated intervention according to their groups allotted. The Sample size was selected on the basis of previous studies where b50 patients in each group were taken.
A thorough pre-anesthetic work up was carried out for all the patients. General anesthesia was induced in all patients with intravenous (IV) propofol, fentanyl and atracurium. Maintenance of anesthesia was done with isoflurane in oxygen and air (50:50). Intra-operatively, IV fentanyl (0.5 mcg/kg) was administered if heart rate (HR) and blood pressure (BP) is N20% of the base line excluding the other causes of increase in HR and BP like raised end tidal carbon dioxide (EtCO2) and due dose of nondepolarizing muscle relaxant. All patients received IV dexamethasone (4 mg) after induction. During intra operative period both the groups received ringer acetate solution (Sterofundin ISO) intravenously @ 100 ml/h as maintenance fluid. Apart from this, patients of group NS received 250 ml of 0.9% normal saline and patients of group D received 5% dextrose @ 100 ml/h started at the time when gall bladder was taken out. It was continued in the postoperative period with the same rate till it gets finished. For the purpose of blinding, the label of the study fluid (5% dextrose or normal saline) was removed by a senior anesthesiologist to prevent observer's bias. The person who was administering the study fluid was kept unaware about the type of study fluid. In the recovery room or in the ward, an independent observer who was not aware of the type of study fluid, noted the numbers of PONV episodes. Parameters like HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), SpO2 (% saturation of hemoglobin), EtCO2, airway pressure (Paw) were noted at time of induction, intubation, after 10 min and then at the difference of 10 min till extubation. All patients received injection paracetamol (15 mg/kg) intravenously at the end of surgery and neuromuscular blockade was reversed with injection neostigmine and glycopyrrolate. All patients were assessed for PONV by using visual analogue scale (VAS) from 0 to 10, where 0 means no nausea and 10 means worst possible nausea or any episode of retching or vomiting. Patients with VAS score of 3 or more received ondansetron 4 mg intravenously as a first line antiemetic treatment. However, if PONV persisted after 30 min after above treatment, then metoclopramide 10 mg was administered intravenously. The VAS score for PONV was recorded after 30 min, 60 min, 90 min, 6 h, and 24 h after patient arrival in PACU. The total amount of rescue antiemetic (intravenous ondansetron in an incremental dose of 4 mg) in 24 h postoperatively was noted for every patient.
Fig. 1. Consort diagram.
A. Mishra et al. / Journal of Clinical Anesthesia 40 (2017) 7–10
Patients were kept in PACU for 6 h after the surgery. After this period patients were shifted to ward and kept there up to 24 h following surgery. The primary outcome of this study was to observe the incidence of PONV in both the groups. The secondary outcome of the study was to find out the consumption of rescue antiemetics, Apfel score, intraoperative opioids and fluids administered in both the groups. 3. Statistical analysis Data analysis was carried out using Stata 12.0 (College station, Texas, USA). The data was presented as number (%) and mean ± standard deviation (SD) as appropriate. The baseline categorical and continuous characteristics were analyzed between the groups using Chi square test/Fisher's exact test and Student's ‘t’ test for independent samples respectively. The primary outcome, incidence of PONV were compared between the two groups using ‘Z’ test and ANCOVA (Analysis of covariance) was carried out to adjust for the imbalance found in total intraoperative opioid consumption between the two groups. The results were presented as both unadjusted and adjusted difference in the incidence of PONV and 95% confidence interval. The change in hemodynamic parameters over a period of time between the two groups was assessed using repeated measures ANOVA (Analysis of variance). The p b 0.05 was considered statistically significant. 4. Results There was no significant intergroup difference in the base line characteristics like age, gender, height, weight, ASA status, total duration of surgery/anesthesia, and intraoperative fluid administered (Table 1). The mean body mass index (BMI) of the patients in group NS was 24.37 ± 3.62 kg/m2 while in group D 22.88 ± 2.84 kg/m2. This difference was statistically significant but clinically within the normal range of BMI. The distributions of patients according to smoking status were comparable in both groups. The distribution of patients according to Apfel score was also comparable in both the groups (p value 0.616). In group NS all the patients had low Apfel score while in group D 49 patients had low Apfel score and only one patient had high Apfel score. The mean of total intraoperative opioids used in group NS versus group D were comparable at all time points after adjusting. Adjustment was done using RM ANCOVA (Repeated Measures Analysis of covariance) test (Table 1). Table 1 Demographic characteristics, Apfel score, duration of anesthesia/surgery and total intraoperative opioids and fluids used in both groups. Characteristics
Group NS Mean ± SD
Group D Mean ± SD
p Value
Age (years) Weight (kilograms) Height (centimeters) BMI (kg/m2) Nonsmokers Smokers ASA 1 ASA 2 Male Female Apfel score 0 Apfel score 1 Apfel score 2 Apfel score 3 Apfel score 4 Anesthesia time (minutes) Surgical time (minutes) Total intraoperative opioids (micrograms) Total intraoperative fluids (milliliter)
39.6 ± 11.54 62.22 ± 9.86 159.8 ± 8.40 24.37 ± 3.62 40 (80%) 10 (20%) 40 (80%) 10 (20%) 17 (34%) 33 (66%) 7 (14%) 39 (78%) 4 (8%) 0 (0%) 0 (0%) 67.1 ± 17.41 40 ± 13.28 148.8 ± 33.02
37.42 ± 12.00 57.68 ± 10.03 158.5 ± 10.30 22.88 ± 2.84 42 (84%) 8 (16%) 41 (82%) 9 (18%) 11 (22%) 39 (78%) 6 (12%) 41 (82%) 2 (4%) 1 (2%) 0 (0%) 65.2 ± 14.39 38.7 ± 10.82 134.5 ± 34.14
0.357 0.02⁎ 0.49 0.02⁎ 0.603
0.55 0.59 0.03⁎
611 ± 136.38
605 ± 138.96
0.82
⁎ p b 0.05.
0.799 0.181 0.616
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Table 2 Overall incidence of PONV in both the groups. PONV
Group NS
Group D
p Value
Absent Present Unadjusted difference (95% confidence interval) Adjusted difference (95% confidence interval)
17 (34%) 33 (66%) 38.5 (19.9–56.0)
36 (72%) 14 (28%)
0.001⁎
38.49 (19.47–57.51)
Adjusted for total intraoperative opioids. ⁎ p b 0.05.
Out of total 100 patients, 47 patients (47%) had PONV (Table 2). In group D, 14 patients (28%) had PONV within 24 h of surgery while in group NS, 33 patients (66%) had PONV with a significant p value (p value 0.001). None of the patients had any PONV within first 30 min. Twenty out of 100 patients had PONV score ≥ 3 in first 60 min for which they were given rescue antiemetics. Twenty seven patients had PONV during first 90 min, 16 patients after 120 min and 9 patients after 6 h of surgery. Only 1 patient had PONV after 24 h of surgery (Table 3). Out of the total 14 patients of group D who had PONV, only 3 (6%) patients had to be given 1 repeated doses of ondansetron 4 mg while 11 (22%) patients received only single dose of ondansetron 4 mg to combat PONV. In the NS group 33 (66%) out of 50 patients received rescue antiemetics. In this group 24 patients (48%) received only one dose of ondansetron 4 mg, 7 patients (14%) received one repeated dose of ondansetron while 2 patients (4%) received ondansetron 4 mg + metoclopramide 10 mg. There was only one patient with high Apfel Score while the rest of 99 patients had low Apfel score. Due to this highly uneven distribution in Apfel scoring, analysis could not be done. 5. Discussion The present study is unique in a way that it demonstrates a 38% reduction in PONV in patients receiving perioperative dextrose when compared to patients receiving perioperative normal saline which is the primary outcome of the study. This reduction is even more than that of previous studies. The only difference between the groups was 250 ml of 5% dextrose infusion at the rate of 100 ml/h in group D patients. The secondary outcome of the study which is to find out the consumption of rescue antiemetics in both the groups has also shown better results in the group receiving dextrose. There is 26% reduction in use of single dose of ondansetron 4 mg in dextrose group. None of the patients received metoclopramide injection in dextrose group. In light of its ease, low risk, and benefit to patient care and satisfaction, this therapeutic modality could be considered. Postoperative nausea vomiting is one of the limiting factors in early discharge of daycare surgery patients and is a leading cause of unanticipated hospital admission. Current approaches to prevent and treat PONV are limited and N25% of patients experience PONV within 24 h postoperatively [5]. In fact, PONV can be as frequent as 80% among high-risk patients [6]. Despite this, universal pharmacologic PONV prophylaxis does not seem to be cost effective, and is associated with increased side effects. Adverse effects of these drugs are headache, lightheadedness, dizziness, and constipation (serotonin antagonists) and sedation, lethargy, agitation, extrapyramidal effects, prolonged QT interval (dopamine antagonists). Although some advocate prophylactic antiemetic therapy for high-risk patients, with rescue antiemetic treatment for episodes of PONV, the optimal approach remains still unclear. There are some adjuvant therapies which decrease the incidence of PONV. Various studies identified dehydration as an important factor in the incidence of PONV [16,17]. Lambert K G et al. noted that preoperative fluid bolus using 4-2-1 rule decreases the incidence of PONV significantly [18]. The present study demonstrates a novel and comparatively cheaper method to reduce the incidence of PONV by giving 5% dextrose perioperatively in nondiabetic adult patients undergoing laparoscopic
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A. Mishra et al. / Journal of Clinical Anesthesia 40 (2017) 7–10
Table 3 Patients with PONV in both groups within 24 h of surgery at different time points. Time
30 min 60 min 90 min 120 min 6h 24 h
Group NS No. of patients with PONV N = 50
Group D No. of patients with PONV N = 50
Total No. of patients with PONV N = 100
0 14 17 10 7 1
0 6 10 6 2 0
0 20 27 16 9 1
cholecystectomy. There are some recent studies on preoperative administration of carbohydrate rich drinks and comparison of PONV with fasting patients. Yilmaz N et al. showed that PONV and antiemetic consumption was lower in group with preoperative oral carbohydrate compared to group fasting (p = 0.001) [19]. This result is in contrary to that in 200 women patients in a study by Lauwick SM et al. scheduled for thyroidectomy [20]. This study is supported by another study by Dabu-Bondoc S et al. in which 62 nondiabetic, ASA class I or II nonsmoking outpatients scheduled for gynecologic laparoscopic and hysteroscopic procedures were taken. They concluded that post anesthesia IV dextrose administration resulted in improved PONV management as defined by reductions in antiemetic rescue medication requirements and PACU length of stay [21]. However, results of a similar study done by Patel P et al. on 162 ASA I and II female patients showed that the administration of dextrose during emergence from anesthesia was not associated with a difference in the incidence or the severity of PONV in the first 2 h after anesthesia [22]. Reduced incidence of PONV in dextrose group might be because of caloric supplementation in this group which lowered down postoperative catabolism and insulin resistance and improved patient comfort and thus risk of postoperative nausea and vomiting. It also has some direct local action on the wall of gastrointestinal tract which increases the osmotic pressure and thus reduces muscle contraction. The limitations of the present study are: it was carried out in a single centre in Indian population. Extrapolation of results to the other populations should be guarded. The number of patients in high Apfel group were very less, so the risk association with high and low Apfel score could not be done. Other outcomes like postoperative pain and post discharge nausea and vomiting were not studied. The population taken up for this study is adult population so the results cannot be extrapolated to paediatric age group. 6. Conclusion Perioperative administration of 5% dextrose at 100 ml/h can reduce the incidence of PONV and decrease the consumption of rescue antiemetics in patients 24 h following laparoscopic surgery.
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