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Effect of pre-operative oral carbohydrate loading on recovery after day-case cholecystectomy

A randomised controlled trial

Helminen, Heli; Branders, Hanna; Ohtonen, Pasi; Saarnio, Juha

Author Information
European Journal of Anaesthesiology: August 2019 - Volume 36 - Issue 8 - p 605-611
doi: 10.1097/EJA.0000000000001002
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Abstract

Introduction

In many hospitals it is traditional to fast patients from the night before surgery to reduce the risk of aspiration under anaesthesia. Prolonged fasting can result in considerable discomfort before surgery due to hunger, thirst, anxiety or weakness.1,2 Pre-operative glucose-containing drinks have been shown to relieve some of these undesirable effects of fasting during the waiting period before surgery.2–6

Surgical stress can create a state of insulin resistance which can resemble uncontrolled type 2 diabetes.7,8 Insulin resistance is most pronounced during the first postoperative day but may continue for up to 3 weeks.9 This effect may be significant during the early stages of recovery and ultimately affect the length of hospital stay.10

Pre-operative ingestion of glucose has been shown to reduce postoperative insulin resistance associated with fasting and peri-operative stress.4,10–12 Carbohydrate loading has also been demonstrated to reduce postoperative nausea, vomiting and pain in surgical patients.13–15 Some studies have shown a beneficial impact on length of stay in hospital after major surgery.12,16 However, there are few studies of the benefits of pre-operative carbohydrate loading in patients undergoing day-surgery.15 The importance of the subjective wellbeing and recovery of patients is emphasised in day-surgery where the aim is to attain discharge criteria as soon as possible.

In a previous study, we demonstrated that a glucose-rich drink ingested the night before and on the morning of surgery reduced pre-operative discomfort in American Society of Anesthesiologists (ASA) physical status I to III patients after general surgery.3 In this study, we wanted to further evaluate the effect of carbohydrate loading on the recovery of a uniform set of patients (ASA status I to II) undergoing the same procedure, day-case cholecystectomy. Our hypothesis was that ingestion of a single carbohydrate drink on the morning of surgery would enhance the subjective well being and recovery of the patients, thus reducing the time in hospital.

Methods

Approval for this prospective, randomised study was granted by the Ethical Committee of Oulu University, Oulu, Finland on 28 September 2012 (Ethical Committee 69/2012). Written informed consent was obtained from each patient. It was carried out at the Central Hospital of Seinäjoki and at Oulu University Hospital.

Adults between 18 and 70 years old with ASA physical status I to II who were scheduled for day-case cholecystectomy were included. Patients with bleeding or coagulation disorders, BMI more than 40 kg m−2, dementia and those suffering from insulin-treated diabetes, migraine, Meniere's disease or with history of alcohol or drug abuse were excluded from the study.

Patients were informed of the study at the outpatient clinic once the decision for surgery was made. Sealed envelopes were made using random number allocation and opened by a researcher independent of the clinical team. The patients were randomly assigned to two groups: first, carbohydrate-rich drink (CHD group), second, fasting overnight (fasting group). Patients in the CHD group were instructed to drink 200 ml of a carbohydrate-rich drink (Providextra; Fresenius Kabi Ab, Bad Homburg vor der Höhe, Germany) containing 300 kcal, 67-g carbohydrate and 8-g protein, at home before leaving for the hospital, or by 6 a.m. for surgery scheduled at 8 a.m. or 8 a.m. at the latest for later surgery. All other patients were instructed to take nothing by mouth after midnight on the night before surgery. The nurse giving the instructions to the patients at the outpatient clinic was not otherwise involved in the study.

Upon arrival in hospital the patients scored their subjective sense of discomfort with a visual analogue scale (VAS 0 to 100) and this was repeated during the study. The variables were presented on a separate questionnaire which the patients filled in during the study. Six different sources of discomfort were evaluated: thirst, hunger, dryness of mouth, tiredness, nausea and pain. The variables were evaluated upon arrival at the day-surgery unit, immediately before entering the operating room, 2 and 4 h after surgery and at discharge. Blood glucose levels were measured using fingertip sampling upon arrival at the day-case surgery unit and 2 h after surgery. In the event of an overnight hospital stay, the scores for discomfort were monitored in the morning prior to discharge.

Patients attended the day-case surgery clinic on the morning of surgery. The nurse receiving and interviewing them handed out study questionnaires and instructed them on the use of the VAS for the forms of discomfort. The time of ingestion of the CHD drink was recorded by the nurse, who was not otherwise involved. All other care providers were blinded to the group allocation. All patients were anaesthetised according to the normal practice of each hospital. No premedication was used. Anaesthetic induction was performed with fentanyl, propofol and a muscle relaxant. Anaesthesia was maintained with desflurane and bolus doses of fentanyl or relaxant as needed. The intra-abdominal pressure was maintained at 12 mmHg during laparoscopy. Standard monitoring was used. A 0.9% saline or Ringer solution was administered at a standard rate of 4 to 5 ml kg−1 h−1. At the end of surgery paracetamol (Perfalgan) 1 g, ketoprofen (Ketorin) 100 mg and ondansetron (Zofran) 4 mg were given intravenously. The trochar incisions were infiltrated with bupivacaine 0.5% with adrenaline. In the postoperative care room care was provided by a nurse blinded to the group allocation. Patients with a VAS score more than 3 for pain were given intravenous oxycodone (Oxynorm) 3 to 4 mg or oral 5 to 10 mg. In addition 5 ml × 3 of intravenous metamizol/pitofenone (Litalgin) was administered if required. Patients were allowed to drink water. The 0.9% saline or Ringer's solution was continued until oral intake was possible and in the recovery room food was offered 2 h after surgery at the earliest. The time and amount of fluid ingestion, intake of nutrition, ambulation, requirements for analgesia or antiemetic and discharge were recorded and written on a separate form filled in by the recovery nurse. The discharge criteria were: absence of pain or mild pain or nausea, able to drink, eat and ambulate normally. The number and reasons for not meeting the discharge criteria, such as requiring an overnight stay or re-admission, were also recorded. All questionnaires containing the VAS scores of the patients and the details of recovery were gathered by the recovery nurse after discharge and collected in a separate closed box for the investigators in charge.

Statistical analysis

The sample size calculated on the basis of the pilot study was 53 patients per group (difference between VAS means = 2.05, SD = 2.84, α = 0.05, power = 90% and estimated drop out 20%). The distribution of the predictor variables in case numbers or mean ± SD were calculated. The results of the discomfort variables are presented as median [IQR]. Statistical analyses were performed by the Mann–Whitney test, Pearson χ2 test or Fisher‘s exact test. Repeatedly measured data were analysed by linear mixed model (LMM) using patient's as random effects. Repeatedly measured variables pain and nausea were dichotomised (=0 vs. >0) and were analysed by generalised LMM (GLMM) due to excess zeroes. The reported P values for LMM and GLMM are: Ptime, for change over time; Pgroup, for the average between-group difference; and Ptime×group, for the interaction between time and group. Estimated difference (treatment effect) with 95% confidence interval at 2 and 4 h postoperatively was calculated with LMM, except for pain and nausea, for which Student's t test was used. All analyses were conducted according to the intention-to-treat principle. Statistical analyses were carried out with SPSS (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0; IBM Corp., Armonk, New York, USA and SAS version 9.4; SAS Institute Inc., Cary, North Carolina, USA). The P value less than 0.05 was considered statistically significant.

Results

One hundred and twenty patients were originally asked to participate in the study. Seven declined, leaving 113 for enrolment. Four in the CHD group and one in the Fasting group did not fill in the postoperative questionnaires (Fig. 1). The data were gathered over a period of 3 years, between 2013 and 2016, in the University Hospital of Oulu and the Central Hospital of Seinäjoki.

Fig. 1
Fig. 1:
CONSORT flow diagram.

The groups were comparable for sex ratio, age, ASA physical status, BMI and diabetic status (Table 1). As indicated in Table 2, the fasting time (the time from eating and drinking the night before to induction of anaesthesia) did not differ between groups. Also, there was no difference between groups in the mean waiting time (from arrival at hospital to induction of anaesthesia) (Table 2). 25 (44%) patients in the CHD group and 23 (41%) in the fasting group had a waiting time over 4 h, that is their surgery was not scheduled first in the morning. The median [range] time from drinking the carbohydrate drink to induction of anaesthesia was 3 h.2–7

Table 1
Table 1:
Patient characteristics
Table 2
Table 2:
Fasting times and anaesthetic details

Blood glucose levels did not differ significantly between groups in the waiting period or after surgery (Table 2). There were no significant differences in the duration of anaesthesia or surgery or in the volume of intravenous infusion administered (Table 2). There was no apparent or suspected peri-operative pulmonary aspiration in either group.

The VAS scores for the discomfort variables are shown in Table 3. The highest median VAS scores were seen for thirst before the induction in the fasting group, and for thirst, mouth dryness, tiredness at 2 h after surgery in the both groups. Trend analysis showed significant changes over time in VAS for thirst, hunger, mouth dryness, tiredness and pain in both groups but there was no significant interaction between time and group. The differences between the study groups varied between −9.2 and 4.8 at 2 h and 4 h postoperatively. The VAS scores for nausea were low and were not significantly affected in the postoperative period. Sex and age did not affect the distribution of discomfort variables.

Table 3
Table 3:
Visual analogue scale data for peri-operative discomfort variables

There were no differences between the study groups in the postoperative outcomes or need for analgesia or antiemetic treatment (Table 4). Three patients in the CHD group had postoperative vomiting compared with four in the fasting group. Six patients in the CHD group and seven patients in the fasting group could not go home on the same day. The reasons for the overnight stay in hospital were nausea for four, pain for one and undefined for two patients in the CHD group; nausea for three, pain for one and tiredness for two in the fasting group, respectively. No patient required readmission to hospital.

Table 4
Table 4:
Characteristics of postoperative care and outcomes

Discussion

In this study, pre-operative oral carbohydrate loading did not improve the wellbeing of patients after day-case cholecystectomy. Although there was a significant difference over time for most of the discomfort variables (thirst, hunger, mouth dryness, tiredness and pain) they did not differ between patients receiving a carbohydrate drink compared with those fasting overnight. Also, outcomes, such as recovery time and length of hospital stay did not differ significantly between the study groups.

In previous studies, pre-operative carbohydrate loading has been shown to improve peri-operative well being,2–4 postoperative metabolism such as insulin resistance,4,11,12,17 and to reduce hospital stay.16 Our study failed to show any benefit from carbohydrate loading, which is in accordance with the studies by Mathur et al.18 in colorectal and liver resection patients and Bisgaard et al.19 in cholecystectomy patients. They found no benefit of pre-operative oral carbohydrate treatment on postoperative fatigue, general wellbeing or length of hospital stay. Also, Harsten et al.5 observed only limited benefits from carbohydrate loading in patients undergoing total hip arthroplasty. These contradictory findings may be due to differences in study design, timing and amount of carbohydrate treatment and the surgical procedure. Surgical patients may recover well independent of carbohydrate loading because of the minimally invasive nature of the procedures. Changes in insulin sensitivity have been found to be less affected after laparoscopic than after open cholecystectomy because the surgical trauma is smaller.8 As in our study, Asukara et al.20 detected no improvement in the quality of recovery in patients undergoing minimally invasive body surface surgery. Also, in a meta-analysis by Awad et al.21 no difference in length of stay was found in patients undergoing surgery with an expected hospital stay of 2 days or less.

Postoperative nausea and vomiting are a major cause of discomfort after anaesthesia and may cause prolongation of length of hospital stay or necessitate admission to hospital after day-case surgery.22,23 In a study by Hausel et al.,13 the incidence of PONV was lower in patients receiving a carbohydrate drink compared with those fasting at 12 to 24 h after laparoscopic cholecystectomy. The overall incidence of patients with PONV episodes was 27 to 39% with the highest incidence occurring 0 to 4 h after surgery. Singh et al.15 also found that carbohydrate loading, compared with fasting or a placebo drink, reduced the incidence of postoperative nausea and vomiting, especially in the first 4 h after surgery. In our study, we found no difference between the study groups in the incidence of PONV. Thirty-two per cent of patients in both groups received additional antiemetic treatment for PONV in the recovery room, and of these seven had an episode of vomiting. The overall median VAS scores for nausea were very low in both groups, which may have been partly due to the use of intra-operative antiemetics in all patients, as is our normal practice. On the contrary, our observation time did not extend to the next day, so we cannot say if PONV remained an issue or differed between groups at home. However, the number of patients requiring an overnight stay because of protracted postoperative nausea was the same in both groups.

Postoperative pain may affect wellbeing and the time to discharge after day-surgery. In the study by Singh et al.15 patients taking carbohydrates compared with placebo or fasting showed a decrease in pain scores after cholecystectomy. The authors suggest that this could have been due to the overall decrease in postoperative surgical stress response due to insulin resistance or improved general wellbeing in these patients. Also, in the study by Tran et al.6 in patients receiving a carbohydrate drink or fasting before coronary artery bypass or spinal surgery, a relationship between pre-operative anxiety scores and length of hospital stay was found. Reduction in anxiety may relate to the degree of pain experienced postoperatively.24 In our study, pain scores increased significantly over time in both groups, but we did not detect any differences in VAS scores or the number of patients receiving analgesic treatment postoperatively. We did not measure peri-operative anxiety in our current study but in our earlier study patients receiving carbohydrate loading did not show an increase in pre-operative anxiety levels as opposed to those fasting or receiving intravenous glucose.3 Further studies may be warranted to determine the role of carbohydrate loading on peri-operative anxiety levels and pain perception.

The timing and dose of the carbohydrate drink has varied according to different study designs. In several studies2,11,13,15–19 patients have received a CHD in the evening and in the morning before surgery. However, Gjessing et al.25 found in an animal study that carbohydrate loading in the morning before the operation improves insulin sensitivity 3 h after intake. Carbohydrate loading in the evening offered no benefit the following day. Svanfeldt et al.26 found similar results in their study on healthy volunteers. Thus, the benefits of using carbohydrate loading in the evening before surgery remain controversial. In a retrospective analysis by McCracken and Montgomery27, the incidence of postoperative nausea and vomiting after day-case anaesthesia was reduced when a new policy was adopted that allowed patients to drink unrestricted clear fluids up until the time of transfer to theatre. In recent years, many hospitals have likewise adopted a more liberal approach to pre-operative fasting. In our centres we have advised patients not to take solids after midnight but to drink clear fluids up to 2 h before surgery. We chose to administer the carbohydrate drink in the morning in accordance with this regime so as to emulate our current practice.

The amount of the carbohydrate drink in our current study was smaller (200 ml) than the one we used in our earlier study (400 ml).3 We chose Providextra as it has been used successfully before major surgery for several years in the University Hospital of Oulu. Also, in our earlier study some patients found the amount of 400 ml too large to ingest in a short time. One dose of Providextra is 200 ml of fluid, containing more calories (300 kcal = carbohydrate 67 g) per volume than the drink used in earlier studies.2,11,13,15–19

One of the limitations of this study is that we could not standardise the exact timing of the pre-operative drink. Overall 41 to 45% had a waiting time of over 4 h and the median time from drinking the carbohydrate drink to the initiation of anaesthesia was 3 h. This may have reduced the beneficial effect of the pre-operative drink. Also, we did not follow-up patients after discharge so the long-term effects on the well being of patients could not be evaluated. However, there were no re-admissions after discharge.

We believe that the strength of our study is that we studied ASA I to II patients undergoing the same surgical procedure, day-case laparoscopic cholecystectomy, with a standardised anaesthetic technique and peri-operative care that reflects our daily practice. The variables in the VAS questionnaire were the same as those used in earlier studies.2,3,13,18,19

Many reviews and meta-analyses of pre-operative carbohydrate loading have been published in recent years.28–31 They reveal that loading has a positive influence on postoperative insulin resistance, peri-operative markers of clinical well being and length of stay in patients undergoing major surgery. In a recent study carbohydrate loading led to less postoperative myocardial injury after off-pump artery bypass.17 However, a recent multiple-treatments analysis by Amer et al.32 showed only minor or no significant clinical effects of pre-operative carbohydrate loading over fasting, water or placebo. The primary outcomes in the 43 trials included in the meta-analysis were length of hospital stay and postoperative complication rate and the secondary outcomes were postoperative insulin resistance, vomiting and fatigue. Our study also failed to show any significant postoperative benefits from loading. Several earlier studies have shown a positive effect of carbohydrate loading on the pre-operative well being of patients compared with fasting.2,3 However, one of the major determining factors of pre-operative discomfort is the feeling of thirst,33 which has been shown to be reduced with placebo (clear flavoured drink) just as effectively as with a carbohydrate-rich drink.2,34 We have currently revised our protocol making a pre-operative CHD (costing approximately 2€ per drink in our units) the routine, rather than urging patients to ingest any clear drink 2 h before day-case surgery.

In conclusion, carbohydrate loading as a single pre-operative drink in the morning did not show any clear advantages over fasting in the recovery after day-case cholecystectomy.

Acknowledgements relating to this article

Assistance with the study: none.

Financial support and sponsorship: none.

Conflicts of interest: none.

Presentation: none.

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