Ketamine Sedation After Administration of Oral Contrast: A Retrospective Cohort Study

Discussion

Our results demonstrate a statistically significant increase in vomiting in patients who received oral contrast before ketamine sedation compared with those who were kept NPO in our patient population. NPO guidelines have been examined with regard to safety with other sedative agents. Ziegler et al examined the safety records in 367 patients who received oral contrast material before sedation for abdominal CT with chloral hydrate in 30 patients and pentobarbital in 337. The results showed that vomiting occurred in 4 cases (1%).⁴ Babl et al studied adverse events in nitrous oxide sedation and found that there was no statistically significant difference in emesis rate in patients who met and did not meet fasting guidelines.¹¹ Also, Kharazmi et al in a cohort of 85 patients showed that the practice of administering oral contrast material within 2 hours of propofol sedation for abdominal CT in children seems to be relatively safe compared with those kept traditional NPO for similar procedures.⁵ Its use for induction and maintenance of anesthesia has been associated with a lower incidence of postoperative nausea and vomiting¹²; this finding could be because of propofol’s inherent antiemetic effect. In contrast, ketamine sedation has been shown to be associated with higher rates of vomiting compared with other agents, with rates ranging from 4% to 8% irrespective of fasting status.^3,13,14 This can explain why ketamine when used in a setting of full stomach was associated with a higher rate of vomiting.

Fasting is intended to reduce the risk of pulmonary aspiration of gastric contents and facilitate the safe and efficient conduct of sedation and anesthesia.¹⁵ The emptying of clear liquids follows first-order kinetics; that is, the rate of emptying is proportional to the volume present.¹⁶ Raidoo et al found that in a primate model, the maximum acid aspirate volume that will not cause damage to the lungs is 0.8 mL/kg.¹⁷ Although increased gastric contents theoretically increase the risk of aspiration pneumonia, there is no known gastric fluid volume (GFV) that places a particular patient at clinically relevant risk or eliminates all the risk. GFV has been used as a surrogate marker for pulmonary aspiration risk in studies evaluating fasting protocol safety.^18,19 In our study population, the mean volume of oral contrast ingested less than 1 hour before induction was 228 ± 46 mL. Even though it is not possible to objectively predict GFV from the amount ingested,²⁰ it would be reasonable to assume that the amount of fluid ingested within 57 minutes of induction of sedation can leave a significant amount of contrast in the stomach depending on the rate of gastric emptying.

Ketamine is a unique agent in procedural sedation and analgesia in that it is a “dissociative” anesthetic that functions by blocking communication between the thalamic and limbic regions of the brain, thereby preventing the brain from processing external stimuli.²¹ It provides excellent sedation, amnesia, and analgesia and preserves muscle tone, maintaining protective airway reflexes and spontaneous respiration.^22,23 Although a short-acting sedative is an ideal agent for elective CT scans, during our study period, ketamine was chosen because of previous experience with successful sedations and limited choices for the sedation team.

Although effective for procedural sedation, vomiting with ketamine is frequently encountered. In the largest 2 emergency department (ED) ketamine series, the incidence of predischarge vomiting was 7% and 8%. Green et al analyzed a meta-analysis of a database that included 8282 ketamine sedations from 32 reports. They concluded that the most important independent predictors of emesis were high intravenous dose (initial dose of 2.5 mg/kg or a total dose of 5.0 mg/kg), intramuscular route, and increasing age (peak at 12 years).²⁴ Our cases were sedated with less than 2 mg/kg of ketamine intravenously and mean age of <2 years.

Despite its increased use in ED procedural sedation, clinically apparent pulmonary aspiration has never been reported during procedural sedation in children but vomiting during such sedation could theoretically increase its risk.^7,25 Our study showed no difference in the rate of oxygen desaturation between the oral contrast and NPO groups despite higher rate of vomiting in the oral contrast group sedated with ketamine. Ketamine’s ability to preserve muscle tone, maintaining protective airway reflexes can be a theoretical reason why pulmonary aspiration was not seen even in the presence of higher incidence of vomiting with this agent, although our study was not powered to conclusively prove this.

Patients sedated in clinical departments such as the ED may have rates of gastric emptying that vary from those of healthy patients on whom NPO guidelines are based. Trauma is a frequent and clinically significant cause of gastroparesis or significantly delayed gastric emptying. A death related to the aspiration of contrast material has been reported in an adult who had abdominal CT evaluation for trauma. Several cases of aspiration of contrast material in children who underwent CT as part of a trauma evaluation have also been reported. These cases have spurred much debate concerning the safety of administering enteric contrast material for CT examination of trauma patients.^26–28 Also, Hoffman et al in a study population of 960 patients identified adverse events or complications in 40 (4.2%) sedations. Nine patients became hypoxic, and 2 pediatric cases of aspiration occurred during sedation, both of whom met NPO criteria.²⁹

Multiple patient variables should be considered when sedating pediatric patients. In addition to NPO status, one should be cognizant of the fact that variables, including gastric volume at the time of sedation, agents used for sedation, associated comorbidities that might delay gastric emptying or predispose to emesis, and compromised ability to protect the airway play a role in assessing risk for aspiration.

There are several limitations to this study. The retrospective study design limited the data to what was documented by the sedation service providers. Some adverse events may not have been captured by the current study design because we did not follow up patients once they were discharged from the sedation unit. Adverse events, including emesis, could have occurred on the way home or at home. Patients may have been admitted with complications such as aspiration without our knowledge. Given that all patients were required by our protocol to be at baseline (awake and alert) before discharge, we would not expect any significant adverse events to have occurred after discharge.

One of the main limitations is the small number of patients enrolled relative to the frequency of serious adverse events. In our study, there were no serious adverse events and, in particular, no pulmonary aspirations. Pulmonary aspiration is a rare event. A recent review of aspiration during procedural sedation and analgesia pooled the data on aspiration risk during general anesthesia and found the overall incidence of aspiration to be 1:3, 420.²⁵ Projecting data from the anesthesiology literature, one would need an extremely large denominator for adequate power to ascertain risk factors for aspiration during sedation and analgesia. However, these data are based on patients who fasted in accordance to the national guideline. The results of our study indicate a difference in the rate of vomiting between fasted patients and those who ingested contrast as prescribed before their examination. The absence of aspiration in our study could be due to either a small sample size or ketamine’s ability to preserve muscle tone maintaining protective airway reflexes.

The higher rate of vomiting in the oral contrast group is not easily explained and may be secondary to factors that we did not systematically collect, such as ancillary medications or primary diagnosis. It is interesting that those in the oral contrast group had abdominal masses, which certainly may be a contributor to increased vomiting and may have shown statistical significance if our numbers were larger.

Considering the rare practice of sedating children with a full stomach, it would not be feasible to collect a large sample size sufficiently powered to detect the risk of aspiration. Our data add to the sedation literature and provide numerical data for future meta-analysis.

In conclusion, children who received oral contrast up to 57 minutes before ketamine sedation had a higher rate of vomiting than those who did not receive oral contrast. However, there was no evidence of aspiration, or higher incidence of adverse events such as apnea or oxygen desaturation. We advise consideration of ketamine associated vomiting for patients who require oral contrast within 2 hours before an abdominal CT.