Effect of a Preoperative Proton Pump Inhibitor and Gastroesophageal Reflux Disease on Postoperative Nausea and Vomiting
by
, ,
Young Suk Kwon
1,2
,
Jun Woo Choi
1,
Ho Seok Lee
1,2,
Jong Ho Kim
1,2,
Youngmi Kim
2 and
Jae Jun Lee
1,2,* 1
Department of Anesthesiology and Pain Medicine, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon 24253, Korea
2
Institute of New Frontier Research Team, Hallym University, Chuncheon 24253, Korea
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(3), 825; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030825
Submission received: 20 February 2020
/
Revised: 13 March 2020
/
Accepted: 14 March 2020
/
Published: 18 March 2020
(This article belongs to the Special Issue Gastrointestinal Disorders: Diagnosis, Treatments and Clinical Features)
Abstract
:Postoperative nausea and vomiting (PONV) are common complications after anesthesia, but no study has considered the effects of a proton pump inhibitor (PPI) and gastroesophageal reflux disease (GERD) on PONV at the same time. Thus, we investigated the effects of a PPI and GERD on PONV. Patients aged ≥18 years who underwent general anesthesia between 2010 and 2019 were enrolled. In total, 202,439 patients were included and 21,361 In a multivariate analysis, the OR for PONV was higher in subjects with GERD (OR, 1.157; 95% CI, 1.032–1.298; p = 0.012). The OR was lower for subjects with taking a PPI (OR, 0.890; 95% CI, 0.832–0.953; p < 0.0001). In patients without GERD, the incidence of PONV was lower when lansoprazole (OR, 0.801; 95% CI, 0.718–0.894; p < 0.0001), pantoprazole (OR, 0.856; 95% CI, 0.748–0.980; p = 0.025) and ilaprazole (OR, 0.391; 95% CI, 0.158–0.966; p = 0.042) were taken. However, in GERD patients, all PPIs did not show reducing the incidence of PONV. Taken together, the results show that a lansoprazole, pantoprazole, and ilaprazole reduced PONV in patients without GERD, and PPI could not reduce PONV in patients with GERD.
1. Introduction
Postoperative nausea and vomiting (PONV) is defined as nausea or vomiting that occurs within the first 24–48 h after surgery [1]. PONV is a common complication after anesthesia and surgery, and affected patients may be more troubled by PONV than postoperative pain [2]. In rare cases, PONV may be associated with suture opening, aspiration of gastric contents, and esophageal rupture [1]. Many reports have cited factors that alleviate or exacerbate PONV [1,3,4,5]. Proton pump inhibitors (PPIs) are occasionally used to reduce pH and the amount of gastric acid before general anesthesia, but they may also have an anti-nausea effect [6]. Gastroesophageal reflux disease (GERD), also known as acid reflux, is a disease in which the stomach contents rise into the esophagus and cause symptoms or complications. GERD can lead to abnormal reflux of gastric contents into the esophagus due to failure of the anti-backflow function of the lower esophageal sphincter (LES) [7]. The gastrointestinal tract can be distended after anesthesia and surgery [8,9], and vomiting is likely to occur in situations where there is dysfunction of the LES, such as GERD. GERD itself can also cause nausea [7]. However, few studies have investigated the effects of a PPI and GERD on PONV, and none has considered their effects on PONV at the same time. Thus, we investigated the effects of a PPI and GERD on PONV in a large retrospective study.
2. Materials and Methods
2.1. Patients
This study was approved by the Clinical Research Ethics Committee of Chuncheon Sacred Heart Hospital, Hallym University (IRB No. 2020-01-002). All data were obtained from the Clinical Data Warehouse, which includes data from five hospitals at Hallym University Medical Center.
The subjects were ≥18 years of age and had undergone surgery under general anesthesia at one of the five hospitals of Hallym University Medical Center between January 2010 and December 2019. Exclusion criteria included:
- Reoperation within 24 h
- unconscious patient;
- patients treated with a ventilator after surgery;
- patients with nausea or vomiting before surgery;
- patients with missing data in their medical records; and
- patients with preoperative PPI type changes.
2.2. PONV, PPI, GERD, and Other Variables
PONV was defined as nausea or vomiting within 24 h after surgery. In healthy people, the irreversible binding of a PPI to H+, K+-ATPase results in a high median intragastric pH for 24 h [10]. Therefore, in this study we determined whether subjects were taking a PPI based on the 24-h period before surgery. Indications for PPI use included treatment of GERD, gastric and duodenal ulcer, Helicobacter pylori, and premedication to reduce the risk of aspiration pneumonia before anesthesia in this study. Also, because PPI treatment of GERD for at least 4 weeks is recommended [11], patients diagnosed with GERD within 4 weeks prior to surgery were enrolled as GERD patients. Patients were classified using the 10th International Statistical Classification of Diseases and Related Health Problems. GERD included not only cases of abnormal findings by endoscopy but also those diagnosed with reflux symptoms.
First, we analyzed the effect of GERD and PPI on PONV. We also analyzed known and expected risk factors for PONV, including age, sex, body mass index, anesthesia time, American Society of Anesthesiologists physical status classification, use of N2O, anesthetic maintenance drugs, patient-controlled analgesia (PCA), hypertension, diabetes mellitus, heart disease, cerebral stroke, smoking, opioid use during surgery, steroids, antiemetics, neostigmine, antibiotics, laparoscopic surgery, Levin tubes and transfusions [3,4]. Second, the effect of proton pump inhibitors on PONV was analyzed according to presence or absence of GERD. PPIs included were omeprazole, pantoprazole, lansoprazole, rabeprazole, esomeprazole, dexlansoprazole, and ilaprazole, and the effect of each PPI type on PONV was analyzed.
2.3. Statistics
Continuous data are presented as mean and standard deviation, and categorical data as frequencies and percentages. For continuous data, t-tests were used to compare patients with and without PONV. Categorical data were analyzed using the chi-square test or Fisher’s exact test. The odds ratio (OR) for occurrence of PONV within 24 h after surgery was determined for each variable by logistic regression. Variables selected by forward selection and backward elimination were included in the regression analyses. In the analysis based on presence and absence of GERD, the unadjusted odds ratio and fully adjusted odds ratio for occurrence of PONV according to PPI types were determined. All reported P-values were two-sided, and a p-value < 0.05 was considered significant. SPSS software (version 24.0; IBM Corp., Armonk, NY, USA) was used for all statistical analyses. The data set used in our study is provided in Supplementary Materials File 1.
3. Results
3.1. Study Population
In total, 225,110 patients underwent general anesthesia during surgery between January 2010 and January 2019; 22,671 patients were excluded, and 202,439 patients were included in the analysis. Among the included patients, 21,361 developed PONV within 24 h after surgery; 3537 patients had GERD; 11,111 patients took a PPI before general anesthesia. Table 1 summarizes the demographic characteristics and clinical data of the patients who received general anesthesia during surgery. Significant differences were observed in all variables between the PONV and no-PONV groups (p < 0.05), except age (p = 0.172), GERD (p = 0.264), and Levin tubes (p = 0.574).
3.2. Odds Ratio for PONV
Figure 1 shows the ORs for the occurrence of PONV of each variable, obtained through simple logistic regression. The unadjusted OR for the occurrence of PONV in subjects with taking PPI was 0.899 (95% confidence interval [CI], 0.843–0.959; p = 0.0001) relative to those without taking PPI. The unadjusted ORs for the occurrence of PONV were not significantly different between presence and absence of GERD.
The fully adjusted ORs for the occurrence of PONV of each variable, obtained through a multivariate logistic analysis including all variables, are summarized in Figure 2. The fully adjusted OR for the occurrence of PONV was 1.157 (95% CI, 1.032–1.298; p =0.012) when the subject have GERD. The fully adjusted OR for the occurrence of PONV was 0.890 (95% CI, 0.832–0.953; p = 0.001) when the subject was taking a PPI. The adjusted ORs for GERD and PPI (i.e., adjusted through backward elimination or forward selection of variables) in the logistic regression are summarized in Table 2.
Table 3 shows types of PPI according to presence and absence of GERD. When patients had GERD, the incidence of PONV was lower when lansoprazole (OR, 0.884; 95% CI, 0.795–0.984; p < 0.023), pantoprazole (OR, 0.792; 95% CI, 0.694–0.904; p < 0.0001) and ilaprazole (OR, 0.390; 95% CI, 0.159–0.955; p =0.039) were taken in univariate logistic analysis. The incidence of PONV was lower when lansoprazole (OR, 0.801; 95% CI, 0.718–0.894; p < 0.0001), pantoprazole (OR, 0.856; 95% CI, 0.748–0.980; p = 0.025) and ilaprazole (OR, 0.391; 95% CI, 0.158–0.966; p =0.042) were taken in multivariate logistic analysis. When patients had GERD, there was no significant difference in the incidence of PONV between doses and non-dose at all types of PPI (Table 4).
4. Discussion
Using large data included 202,439 patients, we estimated the effect of GERD and preoperative PPI on occurrence of PONV. When we assessed the odds ratios of occurrence of PONV by GERD and PPI using univariate logistic regression, GERD was not associated with PONV incidence in patients under general anesthesia. In multivariate analysis, however, GERD and PPI were associated with an increase and decrease in occurrence of PONV. Subsequently, we analyzed the effect of each PPI type on occurrence of PONV, and the effect of PPI on the occurrence of PONV differed depending on the presence or absence of GERD.
Many studies have documented the risk factors for PONV among patients who have undergone anesthesia and surgery. Some studies have reported that PONV is associated with both taking a PPI and GERD. Evidence from randomized trials demonstrated that while taking a PPI preoperatively is not associated with the occurrence of PONV [12,13], GERD is a predictor of PONV [14]. Raeder and colleagues reported that esomeprazole was not effective for PONV but could reduce the amount of vomiting [12]. Although their study had included relatively large covariates, it may be difficult to generalize the results because of the high proportion (97%) of women. Female gender is a well-known risk factor for PONV, and this is confirmed in our study. Weilbach and colleagues also reported that prophylactic esomeprazole did not reduce PONV [13]. Their study did not include enough covariates, an extremely large number of women (98.9%), and 43% of all surgeries were gynecological interventions. The results of two studies were in agreement with our findings that esomeprazole did not affect the occurrence of PONV. However, it is difficult to conclude that all PPI does not reduce PONV in patients who have undergone general anesthesia.
PPIs inhibit gastric H+, K+-ATPase through covalent bonding to cysteine residues in the proton pump [15]. H+, K+-ATPase is involved in the last stage of acid secretion, and inhibitors of this enzyme are more effective than receptor antagonists for suppressing gastric acid secretion [16]. PPIs may have an anti-nausea effect because receptors in the gastric wall play a role in the feeling of nausea, by mediating input to the nausea-vomiting center in the midbrain received through the vagus nerve [6]. However, GERD patients receiving preoperative PPIs did not reduce the occurrence of PONV in this study. Lansoprazole, pantoprazole and ilaprazole have been shown to reduce the incidence of PONV in patients without GERD in this study. PPIs such as esomeprazole are more effective at controlling gastric acid than first-generation PPIs such as lansoprazole and pantoprazole [17,18]. Other mechanisms besides PPI’s gastric acid regulation may be associated with PONV. More research is needed on these results.
Ilaprazole was associated with the lowest probability of PONV. Most PPIs can result in clinically significant drug interactions that result from the suppression or induction of CYP2C19 as well as CYP3A4 due to other concomitant medications [19]. Midazolam and diazepam, which are metabolized by CYP enzymes, have many clinically significant interactions with inhibitors and inducers of CYP3A4 and 2C19. In addition to pharmacokinetic interactions, benzodiazepines have synergistic interactions with other hypnotics and opioids [20]. Because the metabolic process through CYP3A4/5 [21], ilaprazole may have little effect on the metabolism of benzodiazepine.
GERD is a long-term condition in which the stomach contents rise in the esophagus, causing symptoms or complications [22]. GERD is characterized by symptoms of heart burn, chest pain, regurgitation, and dysphagia, and can also cause nausea or vomiting on its own [23,24]. Anesthesia causes gastrointestinal distension [9], which can increase abdominal pressure and reflux. In turn, reflux is associated with nausea and vomiting [24,25]. An adaptive change in the tone of low esophageal sphincter occurs with a general increase in abdominal pressure [26]. However, the adaptive response to increased intra-abdominal pressure is abnormally low in patients with symptoms of reflux, including GERD patients [27].
We have observed a decrease in PONV in many patient populations during our clinical practice, in contrast to clinical trials. It can be argued that patients enrolled in clinical trials may not represent patients who actually present to the clinic [28]. Our study enrolled more than 200,000 patients; our population may be more representative sample of patients undergoing general anesthesia, referred for the assessment of PONV, than those of a number of randomized controlled trials that previously evaluated the associations of PONV with PPI use or GERD.
The current study reinforces previous findings in several important respects. First, PPI use and GERD are closely associated with PONV. GERD increases the incidence of PONV. While some PPIs reduced the incidence of PONV in patients without GERD, PPI does not reduce the incidence of PONV in patients with GERD. Second, we focused on patients who had undergone general anesthesia, and so reported the risk for PONV according to general anesthetic agents. In addition, covariates included diseases such as hypertension, heart disease, and stroke, which have not previously been associated with PONV.
The major limitation of this study was that the group assignment was not randomized according to PPI use and GERD. The utility of observational studies for evaluating the effect of taking a PPI and GERD on PONV is controversial [29], although several studies have suggested that observational designs are not likely to produce misleading or biased results [30,31,32]. Nevertheless, it should be acknowledged that observational studies can only partially control for confounders, and should only use instruments that can be adjusted accordingly. Other limitations of our study also included a lack of on indications for PPI therapy, the types and amounts of opioids used, and on adjustments to the PCA rate, which are important risk factors for PONV. Lack of information can lead to potential heterogeneity of patient characteristics.
5. Conclusions
This study included a large number of patients and many risk factors for PONV, and also controlled for the effects of confounding variables through multivariate analyses Preoperative administration of a lansoprazole, pantoprazole and ilaprazole reduced PONV in patients without GERD. GERD may increase PONV, GERD patients did not reduce the incidence of PONV even when taking PPI. Therefore, our findings provide additional support that GERD is associated with increasing PONV and preoperative esomeprazole is not effective at reducing PONV. However, future prospective, population-based studies are needed to investigate the association between preoperative use of lansoprazole, pantoprazole and ilaprazole, and its impact on reducing PONV.
Supplementary Materials
The following are available online at https://0-www-mdpi-com.brum.beds.ac.uk/2077-0383/9/3/825/s1.
Author Contributions
Conceptualization, Y.S.K. and J.J.L.; methodology, Y.K.; provision of software, J.H.K.; validation, Y.S.K., J.H.K. and J.J.L.; formal analysis, Y.S.K.; investigation, H.S.L. and J.W.C.; resources, H.S.L.; data curation, J.W.C.; writing—original draft preparation, Y.S.K.; writing, reviewing, and editing, J.J.L.; data visualization, J.H.K.; project supervision, Y.K.; project administration, J.J.L.; funding acquisition, J.J.L. All authors have read and agreed to the published version of the manuscript.
Funding
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9E8049714 and 2017M3A9E8033205), South Korea.
Conflicts of Interest
The authors declare no conflicts of interest.
References
- Pierre, S.; Whelan, R. Nausea and vomiting after surgery. Contin. Educ. Anaesth. Crit. Care Pain 2012, 13, 28–32. [Google Scholar] [CrossRef] [Green Version]
- Koivuranta, M.; Läärä, E.; Snåre, L.; Alahuhta, S. A survey of postoperative nausea and vomiting. Anaesthesia 1997, 52, 443–449. [Google Scholar] [CrossRef] [PubMed]
- Watcha, M.F.; White, P.F. Postoperative Nausea and Vomiting: Its Etiology, Treatment, and Prevention. Anesthesiol. J. Am. Soc. Anesthesiol. 1992, 77, 162–184. [Google Scholar] [CrossRef] [PubMed]
- Gan, T.J. Risk Factors for Postoperative Nausea and Vomiting. Anesth. Analg. 2006, 102, 1884–1898. [Google Scholar] [CrossRef] [PubMed]
- Apfel, C.C.; Stoecklein, K.; Lipfert, P. PONV: A problem of inhalational anaesthesia? Best Pract. Res. Clin. Anaesthesiol. 2005, 19, 485–500. [Google Scholar] [CrossRef]
- Smith, G.; Ng, A. Gastric reflux and pulmonary aspiration in anaesthesia. Minerva Anestesiol. 2003, 69, 402–406. [Google Scholar]
- Stefanidis, D.; Hope, W.W.; Kohn, G.P.; Reardon, P.R.; Richardson, W.S.; Fanelli, R.D.; Committee, S.G. Guidelines for surgical treatment of gastroesophageal reflux disease. Surg. Endosc. 2010, 24, 2647–2669. [Google Scholar] [CrossRef]
- Mythen, M.G. Postoperative gastrointestinal tract dysfunction. Anesth. Analg. 2005, 100, 196–204. [Google Scholar] [CrossRef]
- Foldes, F.F.; Kepes, E.R.; Arthur, G. Severe gastrointestinal distension during nitrous oxide and oxygen anesthesia. JAMA 1965, 194, 1146–1148. [Google Scholar] [CrossRef]
- Shin, J.M.; Sachs, G. Pharmacology of proton pump inhibitors. Curr. Gastroenterol. Rep. 2008, 10, 528–534. [Google Scholar] [CrossRef] [Green Version]
- Farrell, B.; Pottie, K.; Thompson, W.; Boghossian, T.; Pizzola, L.; Rashid, F.J.; Rojas-Fernandez, C.; Walsh, K.; Welch, V.; Moayyedi, P. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can. Fam. Physician 2017, 63, 354–364. [Google Scholar] [PubMed]
- Raeder, J.; Dahl, V.; Bjoernestad, E.; Edlund, G.; Modin, S.; Naucler, E.; Bergheim, R.; Kilhamn, J. Does esomeprazole prevent post-operative nausea and vomiting? Acta Anaesthesiol. Scand. 2007, 51, 217–225. [Google Scholar] [CrossRef] [PubMed]
- Weilbach, C.; Kahler, K.; Thissen, U.; Rahe-Meyer, N.; Piepenbrock, S. Esomeprazole for the prevention of postoperative nausea and vomiting. A randomized, placebo-controlled trial. Eur. J. Anaesthesiol. 2006, 23, 338–340. [Google Scholar] [CrossRef] [PubMed]
- Powell, P.W.W.; Vasudevan, M.; Rall, M.; Carrithers, J.A. Gastroesophageal Reflux Disease as a Predictor for Post Operative Nausea and Vomiting. In Proceedings of the 2010 Annual Meeting of the American Society of Anesthesiologists, San Diego, CA, USA, 16–20 October 2010; p. A213. [Google Scholar]
- Sachs, G.; Shin, J.M.; Howden, C.W. Review article: the clinical pharmacology of proton pump inhibitors. Aliment. Pharmacol. Ther. 2006, 23, 2–8. [Google Scholar] [CrossRef] [PubMed]
- Fellenius, E.; Berglindh, T.; Sachs, G.; Olbe, L.; Elander, B.; Sjostrand, S.E.; Wallmark, B. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature 1981, 290, 159–161. [Google Scholar] [CrossRef] [PubMed]
- Miner, P.; Katz, P.O.; Chen, Y.; Sostek, M. Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: A five-way crossover study. Am. J. Gastroenterol. 2003, 98, 2616–2620. [Google Scholar] [CrossRef]
- Röhss, K.; Lind, T.; Wilder-Smith, C. Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with gastro-oesophageal reflux symptoms. Eur. J. Clin. Pharmacol. 2004, 60, 531–539. [Google Scholar] [CrossRef]
- Li, X.-Q.; Andersson, T.B.; Ahlström, M.; Weidolf, L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab. Dispos. 2004, 32, 821–827. [Google Scholar] [CrossRef]
- Olkkola, K.T.; Ahonen, J. Midazolam and other Benzodiazepines. In Modern Anesthetics; Schüttler, J., Schwilden, H., Eds.; Springer: Berlin/Heidelberg, Germany, 2008; pp. 335–360. [Google Scholar]
- Seo, K.A.; Lee, S.J.; Kim, K.B.; Bae, S.K.; Liu, K.H.; Kim, D.H.; Shin, J.G. Ilaprazole, a new proton pump inhibitor, is primarily metabolized to ilaprazole sulfone by CYP3A4 and 3A5. Xenobiotica Fate Foreign Compd. Biol. Syst. 2012, 42, 278–284. [Google Scholar] [CrossRef]
- Kahrilas, P.J.; Shaheen, N.J.; Vaezi, M.F. American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease. Gastroenterology 2008, 135, 1392–1413. [Google Scholar] [CrossRef]
- Koek, G.; Tack, J.; Sifrim, D.; Lerut, T.; Janssens, J. The role of acid and duodenal gastroesophageal reflux in symptomatic GERD. Am. J. Gastroenterol. 2001, 96, 2033–2040. [Google Scholar] [CrossRef] [PubMed]
- Brzana, R.J.; Koch, K.L. Gastroesophageal reflux disease presenting with intractable nausea. Ann. Intern. Med. 1997, 126, 704–707. [Google Scholar] [CrossRef]
- Gill, S.K.; Maltepe, C.; Koren, G. The effect of heartburn and acid reflux on the severity of nausea and vomiting of pregnancy. Can. J. Gastroenterol. Hepatol. 2009, 23, 270–272. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cotton, B.; Smith, G. The lower oesophageal sphincter and anaesthesia. Br. J. Anaesth. 1984, 56, 37–46. [Google Scholar] [CrossRef] [PubMed]
- Lind, J.; Crispin, J.; McIver, D. The effect of atropine on the gastroesophageal sphincter. Can. J. Physiol. Pharmacol. 1968, 46, 233–238. [Google Scholar] [CrossRef] [PubMed]
- Moses, L.E. Measuring effects without randomized trials? Options, problems, challenges. Med. Care 1995, 33, As8–As14. [Google Scholar]
- Pocock, S.J.; Elbourne, D.R. Randomized trials or observational tribulations? Mass Med. Soc. 2000, 342, 1907–1909. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Concato, J.; Shah, N.; Horwitz, R.I. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N. Engl. J. Med. 2000, 342, 1887–1892. [Google Scholar] [CrossRef] [Green Version]
- Benson, K.; Hartz, A.J. A comparison of observational studies and randomized, controlled trials. N. Engl. J. Med. 2000, 342, 1878–1886. [Google Scholar] [CrossRef]
- Lauer, M.S. Primary angioplasty—Time is of the essence. JAMA 2000, 283, 2988–2989. [Google Scholar] [CrossRef]
Figure 1.
Unadjusted odds ratios for the occurrence of PONV of each variable obtained through logistic regression. GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; BMI, body mass index; ASA, American Society of Anesthesiologist physical status; Iso., isoflurane; Sevo., sevoflurane; Des., desflurane; Enf., enflurane; PCA, patient-controlled analgesia; LS, laparoscopic; OR, odds ratio; CI, confidence interval; PONV, postoperative nausea and vomiting.
Figure 1.
Unadjusted odds ratios for the occurrence of PONV of each variable obtained through logistic regression. GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; BMI, body mass index; ASA, American Society of Anesthesiologist physical status; Iso., isoflurane; Sevo., sevoflurane; Des., desflurane; Enf., enflurane; PCA, patient-controlled analgesia; LS, laparoscopic; OR, odds ratio; CI, confidence interval; PONV, postoperative nausea and vomiting.
Figure 2.
Adjusted odds ratios for the occurrence of PONV of each variable obtained through multivariate logistic regression including all variables. GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; BMI, body mass index; ASA, American Society of Anesthesiologist Physical Status; Iso., isoflurane; Sevo., sevoflurane; Des., desflurane; Enf., enflurane; PCA, patient-controlled analgesia; LS, laparoscopic; OR, odds ratio; CI, confidence interval; PONV, postoperative nausea and vomiting.
Figure 2.
Adjusted odds ratios for the occurrence of PONV of each variable obtained through multivariate logistic regression including all variables. GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; BMI, body mass index; ASA, American Society of Anesthesiologist Physical Status; Iso., isoflurane; Sevo., sevoflurane; Des., desflurane; Enf., enflurane; PCA, patient-controlled analgesia; LS, laparoscopic; OR, odds ratio; CI, confidence interval; PONV, postoperative nausea and vomiting.
Table 1.
Demographic characteristics and clinical data of patients undergoing general anesthesia.
| No-PONV (n = 181,078) | PONV (n = 21,361) | p-Value | ||
|---|---|---|---|---|
| Mean age (y) | 49.2 ± 16.8 | 49.3 ± 16.1 | 0.172 | |
| Women | 90,677 (50.1%) | 15,947 (74.7%) | <0.0001 | |
| Mean BMI | 24.2 ± 3.8 | 23.8 ± 3.7 | <0.0001 | |
| Mean anesthesia time (min) | 136.7 ± 93.0 | 154.9 ± 90.9 | <0.0001 | |
| ASA physical status | 1 | 77,889 (43.0%) | 9408 (44.0%) | 0.001 |
| 2 | 82,280 (45.4%) | 9680 (45.3%) | ||
| 3 | 19,731 (10.9%) | 2146 (10.0%) | ||
| 4 | 1171 (0.6%) | 126 (0.6%) | ||
| 5 | 7 (0.0%) | 1 (0.0%) | ||
| N2O | 46,680 (25.8%) | 4494 (21.0%) | <0.0001 | |
| Anesthetic maintenance agent | Isoflurane | 30,114 (16.6%) | 3281 (15.4%) | <0.0001 |
| Sevoflurane | 102,197 (56.4%) | 12,156 (56.9%) | ||
| Desflurane | 39,766 (22.0%) | 5057 (23.7%) | ||
| Enflurane | 464 (0.3%) | 77 (0.4%) | ||
| Propofol | 8,537 (4.7%) | 790 (3.7%) | ||
| GERD | 3184 (1.8%) | 353 (1.7%) | 0.264 | |
| PPI | 10040 (5.5%) | 1071 (5.0%) | 0.001 | |
| PCA | 78,560 (43.4%) | 14,311(67.0%) | <0.0001 | |
| Hypertension | 43,951 (24.3%) | 4809 (22.5%) | <0.0001 | |
| Diabetes mellitus | 20,659 (11.4%) | 2027 (9.5%) | <0.0001 | |
| Heart disease | 7983 (4.4%) | 845 (4.0%) | 0.002 | |
| Cerebral stroke | 4952 (2.7%) | 424 (2.0%) | <0.0001 | |
| Smoking | 34,950 (19.3%) | 1836 (8.6%) | <0.0001 | |
| Opioid use during surgery | 155,963 (86.1%) | 19,316 (90.4%) | <0.0001 | |
| Steroid | 12,659 (7.0%) | 916 (4.3%) | <0.0001 | |
| Antiemetics | 99,149 (54.8%) | 15,780 (73.9%) | <0.0001 | |
| Neostigmine use | 48,579 (26.8%) | 6780 (31.7%) | <0.0001 | |
| Levin tube | 3638 (2.0%) | 417 (2.0%) | 0.574 | |
| Laparoscopic surgery | 38,401 (21.2%) | 5616 (26.3%) | <0.0001 | |
| Transfusion | 7780 (4.3%) | 1089 (5.1%) | <0.0001 | |
| Antibiotics | 157,137 (86.8%) | 18,405 (86.2%) | 0.012 |
Postoperative nausea and vomiting; BMI, body mass index; ASA, American Society of Anesthesiologists; GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; PCA, patient-controlled analgesia. Data are numbers of participants unless otherwise specified.
Table 2.
Adjusted odds ratios for the occurrence of PONV by GERD and PPI status.
| Odds Ratio (95% CI) | p-Value | ||
|---|---|---|---|
| Adjusted through forward selection of variables | GERD (-) | Reference | |
| GERD (+) | 1.157 (1.031–1.297) | 0.013 | |
| PPI (-) | Reference | ||
| PPI (+) | 0.891 (0.833–0.954) | 0.001 | |
| Adjusted through backward elimination of variables | GERD (-) | Reference | |
| GERD (+) | 1.157 (1.032–1.297) | 0.013 | |
| PPI (-) | Reference | ||
| PPI (+) | 0.890 (0.832–0.953) | 0.001 |
GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; CI, confidence interval. Forward selection variables: PPI, GERD, age, sex, BMI, anesthesia time, American Society of Anesthesiologist Physical Status, nitrous oxide, anesthesia maintenance agent, patient-controlled analgesia, diabetes mellitus, cerebral stroke, smoking, steroid, opioid, antiemetics, neostigmine, Levin tube, laparoscopic surgery, and transfusion. Backward elimination variables: PPI, GERD, age, sex, BMI, anesthesia time, American Society of Anesthesiologist Physical Status, nitrous oxide, anesthesia maintenance agent, patient-controlled analgesia, hypertension, diabetes mellitus, cerebral stroke, smoking, steroid, opioid, antiemetics, neostigmine, Levin tube, laparoscopic surgery, transfusion, and antibiotics.
Table 3.
Types of PPI according to presence and absence of GERD.
| GERD (−) (n = 198,902) | GERD (+) (n = 3537) | |
|---|---|---|
| Omeprazole | 219 (0.1%) | 26 (0.7%) |
| Pantoprazole | 2873 (1.4%) | 118 (3.3%) |
| Lansoprazole | 4029 (2.0%) | 156 (4.4%) |
| Rabeprazole | 353 (0.2%) | 17 (0.5%) |
| Esomeprazole | 3011 (1.5%) | 156 (4.4%) |
| Ilaprazole | 113 (0.1%) | 4 (0.1%) |
| Dexlansoprazole | 28 (0.0%) | 5 (0.1%) |
GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor.
Table 4.
Unadjusted and fully adjusted odds ratios for the occurrence of PONV by PPI type according to presence and absence of GERD.
Table 4.
Unadjusted and fully adjusted odds ratios for the occurrence of PONV by PPI type according to presence and absence of GERD.
| GERD (−) (n = 198,902) | p Value | GERD (+) (n = 3537) | p Value | ||
|---|---|---|---|---|---|
| Unadjusted | No PPI | Reference | Reference | ||
| OR (95% CI) | Omeprazole | 0.664 (0.399–1.104) | 0.114 | <0.0001 | 0.998 |
| Pantoprazole | 0.792 (0.694–0.903) | <0.0001 | 1.137 (0.631–2.048) | 0.669 | |
| Lansoprazole | 0.884 (0.795–0.984) | 0.023 | 1.350 (0.832–2.192) | 0.224 | |
| Rabeprazole | 0.986 (0.701–1.386) | 0.934 | 1.224 (0.279–5.380) | 0.789 | |
| Esomeprazole | 1.033 (0.920–1.159) | 0.585 | 1.198 (0.723–1.986) | 0.484 | |
| Ilaprazole | 0.390 (0.159–0.955) | 0.039 | <0.0001 | 0.999 | |
| Dexlansoprazole | 0.312 (0.042–2.295) | 0.252 | <0.0001 | 0.999 | |
| Fully adjusted | No PPI | Reference | Reference | ||
| OR (95% CI) | Omeprazole | 0.819 (0.488–1.373) | 0.449 | <0.0001 | 0.998 |
| Pantoprazole | 0.856 (0.748–0.980) | 0.025 | 1.020 (0.540–1.928) | 0.951 | |
| Lansoprazole | 0.801 (0.718–0.894) | <0.0001 | 1.019 (0.603–1.722) | 0.945 | |
| Rabeprazole | 0.890 (0.628–1.262) | 0.513 | 0.643 (0.138–3.001) | 0.575 | |
| Esomeprazole | 1.085 (0.963–1.223) | 0.180 | 0.982 (0.565–1.706) | 0.948 | |
| Ilaprazole | 0.391 (0.158–0.966) | 0.042 | <0.0001 | 0.999 | |
| Dexlansoprazole | 0.355 (0.048–2.645) | 0.312 | <0.0001 | 0.999 |
GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor; OR, odds ratio. When fully adjusted, variables: types of PPI, GERD, age, sex, BMI, anesthesia time, American Society of Anesthesiologist Physical Status, nitrous oxide, anesthesia maintenance agent, patient-controlled analgesia, hypertension, diabetes mellitus, heart disease, cerebral stroke, smoking, steroid, opioid, antiemetics, neostigmine, Levin tube, laparoscopic surgery, transfusion, and antibiotics.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Kwon, Y.S.; Choi, J.W.; Lee, H.S.; Kim, J.H.; Kim, Y.; Lee, J.J. Effect of a Preoperative Proton Pump Inhibitor and Gastroesophageal Reflux Disease on Postoperative Nausea and Vomiting. J. Clin. Med. 2020, 9, 825. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030825
AMA Style
Kwon YS, Choi JW, Lee HS, Kim JH, Kim Y, Lee JJ. Effect of a Preoperative Proton Pump Inhibitor and Gastroesophageal Reflux Disease on Postoperative Nausea and Vomiting. Journal of Clinical Medicine. 2020; 9(3):825. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030825
Chicago/Turabian StyleKwon, Young Suk, Jun Woo Choi, Ho Seok Lee, Jong Ho Kim, Youngmi Kim, and Jae Jun Lee. 2020. "Effect of a Preoperative Proton Pump Inhibitor and Gastroesophageal Reflux Disease on Postoperative Nausea and Vomiting" Journal of Clinical Medicine 9, no. 3: 825. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030825
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
