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Postoperative Nausea and Vomiting Following General Anaesthesia: A Prospective Study on Surgical Patients in the University of Calabar Teaching Hospital, Calabar, Nigeria

Introduction: Postoperative nausea and vomiting remains a significant problem in our clinical setting. This study at the University of Calabar Teaching Hospital, Calabar in Nigeria aims to investigate the incidence of postoperative nausea and vomiting among gynaecological and non-gynaecological patients undergoing surgery under general anaesthesia, compare the incidence as it affects males and females, identify predisposing factors and recommend preventive measures. Methodology: One hundred and sixty six(166) adult patients aged 18 years and above were recruited prospectively excluding cases of full stomach, patients with nasogastric tubes and those who could not be followed up for 24 hours. The past history of motion sickness and postoperative nausea and vomiting was obtained and documented. General anaesthesia was induced with either sodium thiopentone or ketamine hydrochloride. Maintenance was inhalational with or without a relaxant technique. Intravenous pentazocine and subanaesthetic doses of ketamine were used for intraoperative analgesia. The patients were observed postoperatively and questioned at two hourly intervals for nausea or vomiting and pain was scored using the categorical rating scale. A data sheet was completed at the end of 2 and 24 hours. The data was entered on a microcomputer for analysis with aid of EPI INFO version 6 software. The level of significance was set at 95% confidence interval with P value less than 0.05. Results: The overall incidence of nausea was 11.45% and vomiting 13.35% in the 166 patients studied. There was no significant difference in incidence between the gynaecological and non gynaecological patients. Female patients experienced more postoperative nausea and vomiting than male patients with 11.4% and 18.42% nausea and vomiting. Sodium thiopentone induction, muscle relaxant use and reversal as well as moderate to severe postoperative pain increased the incidence of PONV Conclusion: The use of prophylactic “balanced antiemesis” in high risk patients, avoidance of muscle relaxant reversal and adequate postoperative analgesia are recommended as preventive measures.


INTRODUCTION
Postoperative nausea and vomiting (PONV) has been associated for many years with the use of general anaesthesia for surgical procedures. Knapp and Beecher gave excellent definitions several years ago of nausea and emesis and these are still useful today [1]. Nausea is described as the desire to vomit without expulsive muscular movements. It is a subjective experience which is expressed by the patient and cannot be evaluated by the observer [1]. Vomiting on the other hand, is the expulsion of stomach content in varying volume and nature. When the stomach contents are not expelled, the expulsive efforts are termed retching. Though retching is indicative of an empty stomach, it is as unpleasant and stressful to the patient as vomiting. Retching and vomiting may be grouped together and termed "emetic episode." [2] In recent years, there has been a general trend towards a decrease in the incidence and intensity of PONV because of the use of less emetic anaesthetic agents, improved pre and postoperative medication, more refined anaesthetic techniques and identification of patient predictive factors [3] Inspite of all these advances, nausea and vomiting still occur as the "big little problem" [4].
Postoperative nausea and vomiting has been identified as an important cause of unplanned admission after day care surgery. The admission may result not only from uncontrolled nausea and vomiting, but also, from prolonged somnolence following treatment with potent antiemetics [5,6].
The factors identified in the triggering of PONV have been subdivided into the following groups with related conditions: A.
Background factors [7,8,9] such as patients' age and sex, habitus, motion sickness, history of PONV, use of antiemetic, full stomach and anxiety.

B.
Anaesthesia and surgery related factors [9] such as preanaesthetic medication, anaesthetic induction agent, type and duration of surgery, anaesthetic maintenance agent, agent for reversal of muscle relaxation, postoperative pain and its relief as well as movement and transportation of the patient.
These diverse causative factors therefore imply that treatment with combinations of different drugs will be essential for the prevention and management of PONV. This study therefore was aimed at investigating the incidence of postoperative nausea and vomiting in patients undergoing surgery under general anaesthesia at the University of Calabar Teaching Hospital, Calabar, Nigeria.

METHODOLOGY
Consecutive adult patients aged 18 years and above scheduled for elective surgery under general anaesthesia were recruited prospectively. Both in-patients and out-patients of American society of Anaesthesiologists (ASA) physical status I-III were studied.
The following patients were excluded from the study: I. Those for emergency procedure or full stomach II. Patients with gastric outlet obstruction III. Patients on antiemetic treatment IV. Patients who required naso-gastric tube for management V. In cases where 24 hour follow up was not possible The patients were reviewed preoperatively during which their demographic data and relevant history were obtained including previous history of postoperative nausea and vomiting or motion sickness. The terms nausea, retching and vomiting were explained to each patient. All patients received atropine premedication.
General anaesthesia was induced with either Ketamine hydrochloride 2 mg/kg intravenously or a sleep dose of Sodium thiopentone. Patients induced with ketamine were given 10mg diazepam just before the induction agent to prevent postoperative hallucinations. The choice of induction agent and anaesthetic technique was at the discretion of the principal anaesthetist in each case. Maintenance was inhalationally by face mask or endotracheal intubation. Intubated patients were allowed to breath spontaneously or paralysed and ventilated. Endotracheal intubation was facilitated by 1mg/kg of suxamethonium chloride. In patients where a relaxant technique was adopted, pancuronium 0.1mg/kg was used. Intraoperative analgesia was achieved with either of pentazocine 30mg at induction and 6mg every 30 minutes or subanaesthetic doses of ketamine 0.5 mg/kg every 20 minutes. Anaesthesia was maintained with 100% oxygen in halothane. Nitrous oxide was not used because it was not available. At the end of surgery, residual muscle relaxant was reversed using premixed 2.5 mg neostigmine and 1.2 mg atropine in all patients who received pancuronium. Postoperative analgesia was prescribed by the surgical team. A data sheet was produced for each patient.
Postoperative Follow-up: in the recovery room, the patients were interrogated and a questionnaire filled. The period was subdivided into 0-2 hours and 2-24 hours. At the end of each interval, an anaesthetic registrar assessed whether retching or vomiting had occurred and asked if the patients felt nauseated. Nausea as explained preoperatively to the patients meant unpleasant sensations at the back of the throat and epigastrium, cold sweating, salivation, disinterest in surroundings and awareness of the urge to vomit. Retching included laboured spasmodic, rhythmic contractions of the diaphragm, chest and abdominal wall muscles. The forceful sustained contraction of the above listed muscles was regarded as vomiting. Patients who had retching with or without vomiting were categorized as having vomiting. The results were scored as none, nausea, and vomiting. Pain was scored as mild, moderate and severe using the categoric rating scale. The single worst score in any of the time periods was used for analysis. The observations were recorded during the first 24 hours postoperatively.
The data were entered on a microcomputer for anlaysis with the aid of EPI-INFO (version 6) epidemiologic statistical software package. Data were analysed both qualitatively and quantitatively. Quantitative data were presented in the form of frequency tables, pie chart and bar charts. Where necessary, categoric variables were compared using chi-square and Fisher's exact tests while student's T test and analysis of variance (ANOVA) was used for the continuous data. The level of significance was set at 95% confidence interval with p value less than 0.05.

RESULTS
A hundred and sixty six patients were studied 56 gynaecological and 110 non gynaecologiccal. The age ranged from 18 to 70 years in the two groups. The mean age in the gynaecology group was 34.4 years (+10. 49) while the mean age of the non-gynaecological patients was 37.8 years (+14.12). There were 52(31.33%) males and 114(68.67%) females. The duration of anaesthesia ranged from 15 to 180 minutes in the gynaecological patients group mean 73.7 (+44. 08). In the non-gynaecological group, the duration ranged from 20 to 315 minutes with a mean of 102.8 (+53.77). The difference was statistically significant P=0.006, using the studentst test and analysis of variance. The mean Packed cell volume (PCV) of the gynaecological patients was 34.8% (+3.4) ranging from 26% to 41%, in the non gynaecological group, it was 37.8% (+4.4) ranging from 21% to 45% Table. 1.
The difference in incidence of nausea and vomiting in the two groups was not statistically significant (p=0.408) as shown in Table 2.
When PONV was evaluated according to sex as shown in table 3, More females had PONV than males and it was significant (p=0.014). Out of the 52 male patients studied, 6(11.54%) had postoperative nausea and 1(1.92%) vomited. In females, 13(11.40%) had postoperative nausea while 21(18.42%) vomited. The results are presented as mean (SD) *P<0.05 The distribution of patients according to surgical types are shown in Fig. 1.  Among  the  female  patients,  56 had gynaecological and 58 non gynaecological surgery. Seven (12.50%) gynaecological and 6(10.31%) non gynaecological females had postoperative nausea while the incidence of vomiting in the 2 groups was 17.86% and 18.97% respectively. The difference was not statistically significant with a p value of 0.93.
Nine patients had past history of PONV, 5 of them had PONV episodes in this study while 4 did not. This was found to be statistically significant with a Fisher exact 2-tailed p value of 0.0419 Table 4. There were 2 patients with a history of motion sickness and 2 of them had nausea postoperatively.
Body mass index (BMI) had no significant effect on the incidence of PONV. Only 10 patients had BMI above 30 and 1 of them had postoperative nausea, while 3 vomited, as shown in Table 5.
One hundred and thirty three were below 50 years of age. Sixteen (12.03%) of them experienced postoperative nausea (5 males and 11 females) while 20 females vomited. The difference in the incidence of PONV between males and females in this age group was statistically significant p= 0.01. This is shown in Fig. 2 This consisted of 1 of the 10 patients who received endotracheal anaesthesia and 3 of the 37 patients who had anaesthesia by face mask. The difference in the incidence of PONV between patients who received muscle relaxant and who did not, was statistically significant (Table 7).   Pentazocine used for intraoperative analgesia was associated with a 15.2% incidence of postoperative nausea and 14.4% vomiting. Subanaesthetic doses of ketamine was associated with 9.76% incidence of vomiting. This difference was statistically significant. P=0.02 (Table 8).
The duration of anaesthesia for 64 patients was 120 minutes or less while for 102 patients it was more than 120 minutes. The influence of the duration of anaesthesia on the incidence of PONV was not statistically significant P=0.08 (Table 9).

DISCUSSION
Postoperative nausea and vomiting (PONV) is one of the most common side effects of general anaesthesia [10]. The commonly reported incidence is between 1 and 43% [10][11][12][13][14]. This study reports the incidence of nausea of 11.45% while that of vomiting is 13.25%. This is lower than the 14.6% for nausea and 19.6% for vomiting reported by Soyannwo and others in Ibadan-Nigeria [15]. The lower incidence may be attributed to the anaesthetic agents used and the selection of patients. Most patients who vomited in the series were given nitrous oxide and pethidine as part of their general anaesthesia. A meta-analysis by Hartung [16] concisely summarized the results of several studies that convincingly argues for a positive association between nitrous oxide use and emesis. There are logical reasons for expecting PONV with nitrous oxide use. Both nitrous oxide and halogenated anaesthetics decrease lower oesophageal sphincter tone. Any of these agents may facilitate gas entering the stomach during assisted mask ventilation. Belching, flatus, and gastric distention could then promote postoperative vomiting.
The patients in this study had routine overnight preoperative fast for elective surgery as practiced in our centre while the Ibadan study consisted of both fasted and unfasted patients for elective and emergency surgery respectively. The incidence rates reported both in this study and that of Ibadan, are however, lower than that reported in many Caucasian studies. Racial differences may play a role in the reduced incidence of PONV in Africans, [15,17] Bassey while studying gastroesophageal reflux found that, the lower oesophageal sphincter in Nigerians lies completely in the intra-abdominal position while that of Caucasians lies astride the oesophageal hiatus [18]. The lower oesophageal sphincter is important because it prevents reflux of gastric contents into the oesophagus and hence regurgitation or vomiting with the associated risk of aspiration particularly in recumbent and semiconscious subjects. Inhalational anaesthetics produce a reduction in the lower oesophageal sphincter pressure. This is seen in nitrous oxide with oxygen and is enhanced by the presence of halothane or enflurane [19].
It is a recognized fact that preoperative fasting reduces the incidence of regurgitation and aspiration during general anaesthesia [11]. A relatively empty stomach will not enhance vomiting even though nausea may be felt by the patient [10]. The patient with a full stomach is susceptible to postoperative emesis. Eating and digestion trigger the release of gastrointestinal tract hormones that may sensitize the area postrema in the brain stem and facilitate emesis [20].
Gynaecological patients have been reported in several other studies to exhibit a high incidence of PONV [21,22]. This study revealed that a greater percentage of gynaecological patients experienced PONV than their nongynaecological counterparts.  However, the difference between gynaecological and non-gynaecological patients in this study was not statistically significant. Incidences as high as 58% have been reported following major gynaecological surgeries [9] Visalyaputra et al. [23] reported 32% incidence of nausea in patients for gynaecological laparoscopy while vomiting occurred in 35% of cases in a study conducted in Thailand. In this study, 12.5% of the gynaecological patients had only nausea while vomiting occurred in 17.86% cases. Women are 2 -4 times more likely to suffer PONV than men, and their symptoms may be more severe [23] Our study confirms this finding as evident by postoperative vomiting and nausea of 18.42% and 11.40% respectively in women. The incidence of postoperative nausea and vomiting in males taken separately was 11.54% and 1.92% respectively. The greater incidence and severity of PONV in women may be linked to female hormones, as it has been found that most PONV occurs in the luteal phase of menstrual cycle [7][8][9]. There is no gender difference of PONV in children and elderly [7][8][9]. In our study, women below 50 years had 20.41% incidence of postoperative vomiting and 11.22% incidence of nausea while older women had a 12.5% incidence of vomiting and 6.25% of nausea. The mean menopausal age in our environment has been given as 48 years [24]. From this study, PONV appears to occur more frequently among premenopausal women.
Postoperative pain, particularly visceral and pelvic is associated with PONV [7][8][9]. In this study, there appeared to be a significant relationship between the severity of pain and the occurrence of PONV. The incidence of postoperative nausea and vomiting increased progressively with the severity of pain. Opioids are used to relieve moderate to severe pain but nausea and vomiting are their unwanted side effects. In the presence of severe pain however, opioids rather than acting as a causative factor of PONV, may help to ameliorate the severity [9,25,26]. Throughout the period of this study, potent opioids such as pethidine, morphine, fentanyl and alfentanil were unavailable. Pentazocine and subanaesthetic doses of ketamine were used for intraoperative analgesia. Pentazocine was associated with a higher incidence of PONV than ketamine. Pentazocine is an opioid agonist-antagonist and partial agonist. It has powerful agonistic actions at kappa opioid receptors as well as weak antagonist action at delta and mu receptors [25]. Nausea and vomiting are reported among the side effects of pentazocine but it is said to be less common than morphine.
The rate of recovery from anaesthesia also affects the incidence of PONV as sedation itself suppresses the emetic reflex [9]. Hence if recovery is rapid, the patient may reach a state of arousal where emesis can be triggered before the emetic stimuli have subsided. In addition, when the patient becomes conscious, he will be aware of his condition and able to perceive and report nausea and pain. There may also be mismatched visual and vestibular inputs. In addition, the feeling of being out of control of the body, lightheaded and dizzy can make some patients anxious. Removal of such inputs may go some way to explaining why long periods of postoperative sleep may reduce the incidence of PONV. In this study, the use of sodium thiopentone for induction was associated with a higher incidence of PONV than ketamine hydrochloride. This differs from the observation of Thompson et al who found that ketamine is associated with more postoperative emesis than thiopentone or propofol [27]. Watcha and colleagues in 1992 however, pointed out that the frequent assumption that ketamine causes postoperative emesis could not be supported [28]. Boysen et al. [29] have shown a higher incidence of PONV with thiopentone induction when compared with propofol [30]. Propofol has been recommended for day care procedures because of prompt recovery and its antiemetic property.
Patients paralysed with pancuronium in this study, were more likely to have PONV than those who were not paralysed (P=0.004). Muscle relaxants on their own do not have effects on PONV [25]. Antagonism of residual neuromuscular block with a mixture of neostigmine and atropine increased emesis despite the antiemetic action of atropine. In this study, all the 119 patients who received pancuronium were given neostigmine and atropine at the end of surgery to reverse its action. Neostigmine has been said to have significant emetic properties [31]. It is possible that its use caused the increased incidence of PONV observed among the patients who were paralysed. The presence of an endotracheal tube even without the use of muscle relaxants and subsequent reversal contributes to emesis in the postoperative period even though the tube is removed. This is induced by mechanical stimulation of the pharynx resulting in activation of glossopharyngeal afferents projecting to the brain stem. It has been reported that PONV is greater in patients maintained with an orotracheal tube than with a nasotracheal tube. This difference is ascribed to the angle at which the tube impacts the pharynx and presumably relates to different regional sensitivities for evoking the gag reflex from the pharynx [9].
The experienced anaesthetist has fewer patients who suffer PONV than the inexperienced. This may result from a tendency of the inexperienced to maintain deeper levels of anaesthesia. Manual ventilation of the lungs using a face mask before tracheal intubation was associated with more nausea and vomiting when it was performed by an inexperienced anaesthetist compared with an experienced one [32]. This effect persisted for up to 6 hours after operation. The authors suggested that it may result from inadvertent distension of the stomach with anaesthetic gases. In this study, there was a 1.81% incidence of nausea and 4.22% incidence of vomiting in the first 2 postoperative hours. This constituted 24.39% of the entire PONV recorded in 24 hours. In a paediatric population reported by Amponsah, 31% of PONV occurred in the first 2 hours after surgery [12]. The same author stated that this is a very critical period for patients as they may still be under the influence of anaesthetic drugs with a high risk of aspiration. The fact that postoperative emesis occurs beyond the recovery room emphasizes the need for functional suction machines in surgical wards and competent adults to accompany patients home after day care surgery.
The obese, urology, and otorhinolaryngology patients are commonly held by some authors to have increased incidences of PONV which was not the case in this series. Apfel et al. [9] in a study published in 2012, concluded that there is no or insufficient evidence for a number of commonly held factors, such as preoperative fasting, menstrual cycle, and surgery type, and using these factors may be counterproductive in assessing a patient's risk for PONV.
Regional anaesthesia causes less nausea and vomiting than general anaesthesia though regional anaesthesia does not eliminate PONV [23] Bridenbaugh et al. [30] for instance, reported 38% incidence of nausea and vomiting after general anaesthesia for laparoscopy but only 4% when using epiduaral anaesthesia. Nausea and vomiting also occur following spinal anaesthesia as a result of hypotension and the incidence increases with a high spinal block. Ephedrine is effective in reducing emesis during spinal anaesthesia by preventing hypotension. Most of the nausea and vomiting associated with regional anaesthesia occur intraoperatively, but it may extend into the recovery room phase.
The medical impact of postoperative nausea and vomiting is said to be minor because it never becomes chronic and almost never kills although prolonged vomiting may lead to more serious complications in rare cases. Postoperative nausea and vomiting may have an economic impact. As more patients undergo surgery under day care conditions, the humanitarian and economic implication of PONV are becoming increasingly important [33]. From the patient's perspective, it interferes with the patient's comfort. Surgical patients reported the fear of suffering PONV more often that the fear of postoperative pain [9] Tramer [34]. stated that nausea and vomiting are biologically different phenomena. Nausea is not "a little vomiting". They should be reported and analysed separately.
Data on the risk factors and the underlying risk of PONV usually comes from clinical reports and so there still exists many unanswered questions. Randomized controlled trials on the incidence of PONV give inconsistent results which may be influenced by sex, age, race, nature of surgery and the drugs used [9]. It is still poorly understood why some patients vomit after surgery and others do not under similar conditions. Despite efforts to identify patient dependent and patient independent risk factors for PONV, the true underlying risk of PONV in the individual patient remains unpredictable.

LIMITATIONS OF THE STUDY
Nitrous oxide was not available during the period of this study and so its effect does not form a part of these results. Attempt to use neuromuscular blockers without reversal at the end of surgery was not made. This could have been done using Atracurium which is degraded spontaneously in plasma or by monitoring residual neuromuscular blockade using nerve stimulators. The use of these would have verified or disproved the assertion that neostigmine reversal rather than the use of muscle relaxant increases the incidence of PONV. The effect of regional anaesthesia was not evaluated as the study concentrated on patients given general anaesthesia.

POSSIBILITIES FOR FUTURE RESEARCH
The incidence of PONV needs to be further studied not only in adult patients in Nigeria but also in the paediatric age group and where other techniques of anaesthesia apart from general anaesthesia are employed. The current increased use of regional anesthesia and day case surgeries in our hospital will necessitate further clinical research in PONV and particularly in postdischarge nausea and vomiting (PDNV). The most recent development in PONV pharmacology is Aprepitant (Substance P receptor antagonist which acts by blocking NK 1 receptor). More studies are needed to be conducted for guidelines in our environment for these antiemetics. This will assist in the identification of risk factors with a view to minimizing the incidence. Prevention of PONV will achieve better patient comfort postoperatively.

CONCLUSION
In this study, the overall incidence of postoperative nausea was 11.45% and vomiting 13.25% of the 166 patients studied. There was no significant difference in the incidence of postoperative nausea and vomiting between gynaecological and non gynaecological patients (P=0.408). Sex had more influence on the incidence with females having 11.4% incidence of postoperative nausea and 18.42% operative vomiting while males had 11.54% and 1.92% incidences of postoperative nausea and vomiting respectively. Premenopausal females had a greater incidence of PONV than their postmenopausal counterparts. Sodium Thiopentone induction was associated with a greater incidence of PONV than induction using Ketamine Hydrochloride (P=0.04). Postoperative nausea and vomiting occurred more frequently among patients who were paralysed than those who were not. Moderate to severe postoperative pain increased the incidence of PONV significantly (P=0.007).

SUGGESTIONS
Women especially those who are premenopausal and patients with past history of PONV scheduled for surgery under general anaesthesia should have prophylactic balanced antiemesis preferably before extubation. The use of neuromuscular monitoring devices may eliminate the use of reversal agents and thereby prevent PONV. This is because in the absence of opioids or nitrous oxide, patients given general anaesthesia may have to be paralysed for most procedures except very superficial ones to ensure a smooth anaesthesia and surgery. Adequate postoperative analgesia will also reduce the incidence as pain has been found to be a significant factor in the occurrence of postoperative nausea and vomiting.

CONSENT
All authors declare that informed consent was obtained from all the 166 patients for the purpose of this study.

ETHICAL APPROVAL
The Health Research Ethics Committee of the University of Calabar Teaching Hospital gave approval for this study.