ABSTRACT
Background:
Gastric content regurgitation and aspiration are the dreaded complications of securing the airway. Cricoid pressure hinders intubation and causes lower esophageal sphincter (LES) relaxation. A recent study suggests no added benefit of cricoid pressure in preventing pulmonary aspiration of gastric contents. Metoclopramide increases LES tone, prevents gastroesophageal reflux, and increases antral contractions. Hence, we wanted to study the efficacy of metoclopramide for preventing gastric regurgitation during endotracheal intubation (ETI) in patients presenting to the emergency department (ED).
Methods:
This study was a randomized controlled trial in patients requiring ETI in the ED. The study participants were randomized to receive either metoclopramide (intervention) 10 mg/2 ml intravenous (IV) bolus or a placebo of normal saline (placebo) 2 ml IV bolus 5 min before rapid sequence induction and intubation. The outcome of the study was the visualization of gastric regurgitation at the glottic opening during direct laryngoscopy at the time of intubation.
Results:
Seventy-four study participants were randomized and allocated to the metoclopramide group (n = 37) or placebo group (n = 37). Gastric regurgitation at the glottis was noted in three study participants (8%) in the metoclopramide group, and six (16%) in the placebo group (odds ratio [OR] - 0.456; 95% confidence interval [CI] of 0.105–1.981; P = 0.295). The study participants who were intubated in the first attempt had less gastric regurgitation compared to ≥2 attempts (OR 0.031; 95% CI of 0.002–0.511; P = 0.015).
Conclusion:
There was no decrease in regurgitation with metoclopramide as compared to placebo during ETI in study participants presenting to the ED.
Keywords: Aspiration, endotracheal intubation, gastric regurgitation, metoclopramide
INTRODUCTION
The emergency department (ED) is the first line of contact for most critically ill patients in a healthcare setup.[1] Airway management is essential during the resuscitation of a critically ill patient presenting to an ED.[2] Gastric contents aspiration is one of the complications of securing the airway.[1] Securing the airway may be difficult in the ED as the complete airway evaluation is not possible before laryngoscopy compared to the elective surgical scenario in an operating room.[3,4]
The risk factors for gastric regurgitation are pregnancy, obesity, an unknown fasting status, low gastric pH, increased gastric volume, use of sedatives before intubation, and prolonged intubation time.[5,6,7,8] Cricoid pressure is used by some as it may decrease the incidence of pulmonary aspiration as part of the rapid sequence induction (RSI).[9] However, cricoid pressure application can lead to difficult intubation and relaxation of the lower esophageal sphincter (LES).[10,11] There was no evidence that the application of cricoid pressure reduced aspiration during elective endotracheal intubation (ETI) in patients with microaspiration risk factors.[12]
A recent study showed that there is no added benefit of cricoid pressure in preventing pulmonary aspiration of gastric contents as compared to not applying it.[10] Furthermore, applying cricoid pressure can lead to a decrease in LES pressure and displacement of the esophagus.[13,14] In an observational study conducted on a manikin, only the Sellick position and head down can prevent gastric aspiration, but this position is not feasible for trauma patients.[15]
The role of prokinetic drugs has been studied in preventing gastric regurgitation during emergency surgery.[16] Metoclopramide, a D2 receptor antagonist, increases LES tone, prevents gastroesophageal reflux, and increases antral contractions promoting gastric emptying.[17,18,19] The onset of action of metoclopramide is 1–3 min when administered intravenously.[20] Metoclopramide can increase the LES tone when the cricoid pressure is not applied and does not attenuate the cricoid pressure-induced relaxation of the LES.[11] Metoclopramide reduced aspiration pneumonitis in patients undergoing surgery under general anesthesia.[21] Prophylactic intravenous (IV) metoclopramide and antacids in patients requiring sedation decreased the volume and increased the pH of gastric secretion.[22] To the best of our knowledge, the efficacy of metoclopramide in patients undergoing ETI in ED has not been done. The primary objective was to study the efficacy of metoclopramide for preventing gastric regurgitation during ETI in patients presenting to the ED.
METHODS
This randomized controlled trial was conducted in the ED of All India Institute of Medical Sciences (AIIMS) Bhubaneswar from May 18, 2020, to June 10, 2021. The ethical approval was obtained from the Institutional Ethics Committee of AIIMS Bhubaneswar. The study adheres to the CONSORT 2010 Statement and 2022 extension. The study was registered at Clinical Trials Registry-India.
After obtaining written informed consent from the subject’s surrogate, the study included patients ≥18 years of age that presented to the ED, required ETI, and was known not to have oral intake within 6 h of presentation. Patients with severe respiratory distress requiring emergent intubation, with a positive target sign on gastric ultrasonography, already on metoclopramide for other reasons, a known history of gastroesophageal reflux disease, any history of dysphagia, other esophageal pathology (e.g., strictures), pregnancy, and consent refusal were excluded from the study.
As we could not find any literature regarding the effectiveness of metoclopramide in preventing gastric regurgitation, we did a pilot study to calculate the sample size. Gastric content was detected in 5 (31.25%) and 1 (6.25%) out of 16 study participants in the placebo and metoclopramide groups, respectively. The sample size was calculated using nMaster version 2.0 (CMC, Vellore, Tamil Nadu, India). With the power of 80% and 5% significant level, the sample size was 74 (37 in each group) to detect a difference of 25%.
After considering the inclusion and exclusion criteria, study participants were randomly allocated a 1:1 ratio to either the metoclopramide group or the placebo group. The randomization was generated with a block size of four using StatsDirect 3.0 (StatsDirect Ltd., Wirral, UK). The allocation concealment was achieved using the sequentially numbered, opaque, sealed envelope technique. Once the study participant got enrolled in the study, the nurse on duty was asked to open the envelope and assign the group. In the metoclopramide group, the study participants were administered metoclopramide 10 mg/2 ml IV bolus. Those in the placebo group were administered normal saline 2 ml IV bolus. Each was administered 5 min before RSI and intubation. The clinical physician and the study participants were blinded to the study groups, but the persons analyzing the data were not blinded. About 5 min was allowed for the onset of the action of metoclopramide. Following preoxygenation, study participants were premedicated with fentanyl 2 μg/kg IV bolus, and RSI was performed with etomidate 0.3 mg/kg IV bolus and succinylcholine 1.5 mg/kg IV bolus. The cricoid pressure was not applied during RSI. The gastric regurgitation appearing at the glottic opening was observed during laryngoscopy.
The presence or absence of gastric regurgitation, number of attempts, Cormack–Lehane (CL) grade, and vitals were recorded. The primary outcome was the visualization of gastric regurgitation at the glottic opening. The secondary outcome was to find the correlation between gastric regurgitation with CL grade and more than two intubation attempts. There were no changes to trial outcomes after the trial commencement. The data were analyzed using SPSS version 20.0 (IBM Corp., Armonk, New York, USA). A P < 0.05 was considered statistically significant.
RESULTS
Seventy-four study participants were randomized and allocated to the metoclopramide group (n = 37) and placebo group (n = 37). The study participants included in the study are depicted in the flow diagram [Figure 1]. The baseline variables in both groups are depicted in Table 1. The demographic profile of the study participants was comparable between the groups. The vitals before and after the ETI between the two study groups were comparable [Table 2].
Figure 1.
CONSORT diagram
Table 1.
Demographic profile of the study participants
| Variable | Metoclopramide group (n=37), n (%) | Placebo group (n=37), n (%) | Total (n=74), n (%) | P |
|---|---|---|---|---|
| Age (years), mean (SD) | 50.89 (17.178) | 53.73 (15.194) | 52.31 (16.169) | 0.454 |
| Gender, male | 25 (50) | 25 (50) | 50 (100) | 1.000 |
| Diagnosis | ||||
| Road traffic accident | 10 (27) | 9 (25) | 19 (26) | 0.772 |
| Cerebrovascular accident | 14 (38) | 12 (32) | 26 (35) | |
| Others | 13 (35) | 16 (43) | 29 (39) | |
| Antiemetic drug | 1 (33) | 2 (67) | 3 (100) | 1.000 |
| Indication of intubation | ||||
| Low Glasgow Coma Scale | 30 (81) | 28 (76) | 58 (78) | 0.492 |
| Respiratory failure | 7 (19) | 9 (24) | 16 (22) |
SD: Standard deviation
Table 2.
Vital parameters before and after endotracheal intubation
| Variable | Mean (SD) | Total (n=74), n (%) | P | |
|---|---|---|---|---|
|
| ||||
| Metoclopramide group (n=37) | Placebo group (n=37) | |||
| Vitals before intubation | ||||
| Heart rate (bpm) | 101 (24) | 106 (26) | 104 (25) | 0.406 |
| Systolic BP (mmHg) | 148 (32) | 135 (32) | 142 (32) | 0.093 |
| Diastolic BP (mmHg) | 84 (16) | 80 (15) | 82 (15) | 0.174 |
| Respiratory rate (bpm) | 21 (9) | 18 (7) | 20 (8) | 0.181 |
| SpO2 (%) | 91 (13) | 92 (9) | 92 (11) | 0.614 |
| Vitals after intubation | ||||
| Heart rate (bpm) | 106 (22) | 104 (20) | 105 (21) | 0.711 |
| Systolic BP (mmHg) | 147 (33) | 134 (31) | 140 (33) | 0.079 |
| Diastolic BP (mmHg) | 84 (18) | 81 (16) | 82 (17) | 0.344 |
| Respiratory rate (bpm) | 19 (8) | 19 (4) | 19 (6) | 0.794 |
| SpO2 (%) | 99 (2) | 98 (4) | 98 (3) | 0.057 |
BP: Blood pressure, SpO2: Oxygen saturation, SD: Standard deviation
The variables associated with intubations are depicted in Table 3. Twenty-five (68%) study participants in the metoclopramide group and 23 (62%) in the placebo group had CL Grade I. Thirty-three (89%) study participants in the metoclopramide group and 31 (84%) in the placebo group were intubated on the first attempt. Most study participants were intubated without using a stylet or bougie (90.5%). Gastric regurgitation appeared at the glottis in three study participants (8%) in the metoclopramide group and six study participants (16%) in the placebo group (odds ratio [OR] - 0.456; 95% confidence interval [CI] of 0.105–1.981; P = 0.295). The gastric content regurgitation was not statistically significant between the metoclopramide and placebo groups. In the metoclopramide group, the study participants who were intubated in the first attempt had less gastric regurgitation than two or more attempts [OR 0.031; 95% CI of 0.002–0.511; P = 0.015, Table 4]. However, it was not statistically significant for the CL grade (OR 0.957; 95% CI of 0.078–11.719; P = 0.972). In the placebo group, both the number of attempts (OR 0.007; 95% CI of 0.00–0.125; P < 0.001) and CL grade (P = 0.001) were statistically significant with the presence of gastric regurgitation. No adverse events of metoclopramide were observed, and no failed intubation occurred during the study.
Table 3.
Variables associated with intubation
| Variable | Metoclopramide group (n=37), n (%) | Placebo group (n=37), n (%) | Total (n=74), n (%) | P |
|---|---|---|---|---|
| Presence of regurgitate | 3 (33) | 6 (67) | 9 (100) | 0.295 |
| CL grade | ||||
| Grade I | 25 (68) | 23 (62) | 48 (65) | 0.905 |
| Grade II | 7 (19) | 10 (27) | 17 (23) | |
| Grade III | 5 (13) | 4 (11) | 9 (12) | |
| Grade IV | 0 | 0 | 0 | |
| Number of attempts | ||||
| 1 | 33 (89) | 31 (84) | 64 (86) | 0.496 |
| ≥2 | 4 (11) | 6 (16) | 10 (14) | |
| Stylet or Bougie used | 3 (43) | 4 (57) | 7 (100) | 1.000 |
CL grade: Cormack and Lehane grade
Table 4.
Correlation of metoclopramide/placebo with gastric regurgitation when adjusted for the number of attempts and Cormack and Lehane grade
| Drug | aOR (95% CI) | P |
|---|---|---|
| Metoclopramide | ||
| Number of attempts | 0.031 (0.002-0.511) | 0.015* |
| CL grade | 0.957 (0.078-11.719) | 0.972 |
| Placebo | ||
| Number of attempts | 0.007 (0.000-0.125) | <0.001* |
| CL grade | - | 0.001* |
*P<0.05 means significant. CL grade: Cormack and Lehane grade, CI: Confidence interval, aOR: Adjusted odds ratio
DISCUSSION
This randomized, double-blind trial in study participants undergoing ETI in the ED with RSI did not show any statistically significant difference between the metoclopramide and the placebo groups in preventing gastric regurgitation.
The chances of gastric regurgitation increased with more attempts of intubation. In difficult intubation scenarios, prolonged laryngoscopy time and multiple intubation attempts increase the chances of regurgitation and aspiration. The adverse effects such as aspiration, esophageal intubation, oxygen desaturation, hypotension, dysrhythmia, and cardiac arrest increased with multiple intubation attempts.[8] In our study, the intubation was successful on the first attempt in 86% of cases, similar to the study by Fathil et al.[23] Mort et al. found the incidence of regurgitation was relatively low (2%) for intubation attempts of two or fewer, but it increased tenfold (22%) with three or more attempts. The relative risk for regurgitation was seven times higher in >2 attempts (95% CI of 2.82–10.14). Furthermore, esophageal intubation increased the incidence of regurgitation.[24] A secondary analysis of a prospective Japanese Emergency Airway Network Registry found that the adverse events were more in patients for whom multiple intubations were attempted. The incidence of regurgitation was 5% of all adverse events in three or more intubation attempts versus 1% in two or fewer attempts.[25] There was no failed or esophageal intubation noted in our study.
In our study, we included participants who had <6 h of fasting, and the presence of gastric content was detected by ultrasonography. A fasting period of <6 h from history with additional confirmation by ultrasonography helped us to identify the patients at high risk of regurgitation and aspiration. Ultrasonography can provide accurate qualitative and quantitative information about stomach contents and a risk assessment for pulmonary aspiration of gastric contents.[26]
In our study, most of the study participants intubated in the ED were due to a lower level of consciousness (Glasgow Coma Scale ≤8). This is like a study in which the indications for intubation were airway protection, followed by respiratory failure.[27,28]
The risk of aspiration is higher in patients with a depressed level of consciousness.[29] The risk factors for aspiration are an increased tendency to regurgitate (achalasia, diabetic neuropathy, gastro-esophageal reflux, pregnancy, morbid obesity, and neuromuscular disease), increased gastric content (delayed gastric emptying and full stomach), and impaired airway reflexes (head injury, trauma, and neuromuscular disorders).[30] More than two attempts of ETI were associated with regurgitation but not with the CL grade in our study. This is in contrast to a prospective study in ED.[31] Time taken for intubation and body mass index were not measured in our study. We did not follow-up on the intubated study participants to look for the development of aspiration pneumonia.
CONCLUSION
Our study comparing metoclopramide and placebo for preventing gastric regurgitation showed no significant difference. The incidence of regurgitation was less when the intubation was successful on the first attempt.
Research quality and ethics statement
This study was approved by the Institutional Review Board/Ethics Committee at AIIMS Bhubaneswar (Approval No: IEC/AIIMS BBSR/PG Thesis/2019-20/101; Date: February 24, 2020). The study was registered insert prospectively at Clinical Trials Registry-India (Registration No: CTRI/2020/05/025132; Approval date: May 12, 2020). The authors followed the CONSORT 2010 statement and 2022 extension, during the conduct of this research project.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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