Sedation Practices in Pediatric Extracorporeal Membrane Oxygenation

INTRODUCTION

Extracorporeal membrane oxygenation (ECMO) is a lifesaving treatment that primarily supports respiratory and cardiac functions. The first successful ECMO was conducted in 1972 and subsequently in a neonate in 1975.^1,2 Although initial ECMO trials in adults were not satisfactory, the use of ECMO in the pediatric population has gradually increased with good results.³ The most common indication for ECMO in children is a respiratory failure (congenital diaphragmatic hernia and meconium aspiration syndrome in neonates; pneumonia in childhood) followed by cardiac causes (congenital heart disease, myocarditis, and cardiomyopathy).⁴ The use of cardiac ECMO has gradually increased over time in children. Compared to adults, doing an ECMO in children has multiple issues including smaller size of the child, smaller caliber of the vessels, availability of appropriate ECMO cannulae, and lower blood volume. With advanced technologies and experience, the outcomes in children with ECMO are far better compared to adults.⁵

Critically ill children on ECMO need to be sedated for smooth functioning of the ECMO and other supportive care and to provide comfort to the child. These children have multiple interventions including large bore ECMO cannulae, central line, arterial line, endotracheal tube, multiple infusions, and foley catheter. The metabolism and pharmacokinetics of the drugs change in children on ECMO due to multiple factors including ECMO itself and the presence of other organ dysfunction.⁶ The drugs used for sedation and analgesia vary from center to center in critically ill children as well as in children on ECMO.^7,8 Many centers often use neuromuscular blocking agents (NMBAs) in children on ECMO to assist with these lifesaving interventions. The use of sedatives and analgesics adversely affects outcomes in critically ill children.^9,10 Only a few limited studies evaluated the sedation practices and requirements in patients on ECMO and more so in neonatal and pediatric age groups.^7,11–13 Hence this survey was planned to evaluate the sedation practices in children undergoing ECMO from India.

MATERIALS AND METHODS

The primary objective of the study was to identify the sedation practices in children on ECMO support. The study was conducted through an online survey communicated via an email link and a WhatsApp link. The survey link was sent to the members of the ECMO Society of India. The survey link was also sent to physicians from our contact performing pediatric ECMO. Physicians performing pediatric ECMO were asked to fill out the survey.

The questionnaire was developed based on the previous reviews and experience of the ECMO specialists. The survey had 29 questions in five domains: demographics, drug details, protocols, sedation withdrawal, and outcomes.

We collected the following information from the respondents in each domain:

• Demographics: Name and place of the hospital where the respondent is working, number of years since ECMO program initiation, number of ECMO done since program initiation, number of pediatric (respiratory and cardiac) ECMO done annually, and the nature of the organization.

• Drug details: Group of drugs most commonly used, most common sedative agent and analgesic agent used, frequency of use of NMBAs, and frequency of difficulty in achieving adequate sedation in children on ECMO.

• Protocols and management: Use of protocolized sedation strategy, awake ECMO, sedation cycling, and sedation assessment tools.

• Sedation withdrawal: Tools to assess sedation withdrawal, frequency of sedation withdrawal, and drugs used to treat sedation withdrawal.

• Effects and outcomes: Effect on flow disturbances in ECMO and outcomes including duration of ventilation, duration of pediatric intensive care unit (PICU), and hospital stay.

The Google form for the survey was created using the Google interface. The questions were added as either yes/no type OR multiple‐choice type. For a few questions, space was provided for the respondents to give additional information. A trial run was done to identify any difficulties encountered in completing the online survey and the survey form was modified accordingly. The survey link was sent to the potential participants in December 2023 and kept open for 3 weeks to collect their responses. A reminder was sent after every 7 days. Participation in the survey was voluntary, and no incentives were offered to the participants.

RESULTS

The survey link was sent to 413 members of the ECMO Society of India. We received nineteen completed surveys and were included in the study. We received two responses from adult physicians who were not practicing pediatric ECMO and were excluded.

DISCUSSION

Sedation and analgesia an essential components in the management of critically ill children requiring life support to facilitate ongoing care and children on ECMO are no different. Apart from the pathophysiological alterations seen in critically ill children, children on ECMO have other factors which affect drug metabolism and interactions. These include sequestration of drugs (in the pump, oxygenator, tubings, heat exchanger), increased circulating blood volume, and hemolysis.^6,14 Previous studies have shown that these factors lead to higher requirement of sedatives and analgesics to achieve optimal sedation.

In this survey, we observed that nearly all of the respondents used a combination of sedatives and analgesics for optimal sedation which is consistent with the previous literature.¹⁵ Benzodiazepines were the most commonly used sedatives. However, we noted that 37% of the respondents used dexmedetomidine as the first-line sedative agent. Previous studies on ECMO showed that dexmedetomidine was used as a second-line agent in about 15–35% of patients on ECMO.^11,15 Garcia Guerra G et al. and Bakhsh MA et al. in their survey on sedation practices in critical children noted that dexmedetomidine was the preferred agent after benzodiazepines and opioids.^8,16 This increased use of dexmedetomidine might be due to the recent literature suggesting the efficacy and safety of dexmedetomidine in critically ill children.^17,18 We noted that fentanyl was the most commonly used opioid in about 2/3rd of the respondents. Previously, few studies have shown fentanyl as the most common opioid; whereas in a few studies morphine was the most commonly used opioid in children on ECMO.^7,15 Although fentanyl is known to be highly lipophilic and protein-bound leading to significantly decreased levels in the circulation and requirement of higher doses, it continues to be a commonly used opioid in children on ECMO.

We noted that nearly forty percent of the respondents used NMBAs in all children on ECMO and about one-fourth of the respondents used NMBAs in more than >50% of children. Schneider et al. in the secondary analysis of the RESTORE study, observed that 46% of children who were on NMBAs by day 3 of ECMO OR were deeply sedated (34%).¹¹ Anton-Martin P et al. in their retrospective study evaluating sedation and analgesia in children on ECMO, reported that 37.5% of children required NMBAs even after 24 hours of initiation of ECMO.

Two third of the respondents reported that children on ECMO have greater difficulty in achieving adequate sedation and 42% of the respondents used sedative and analgesic doses higher than the doses used in other critically ill children. Buscher H et al. in an international survey on sedation in VV ECMO in adults, reported that 58% of respondents noted a higher dose requirement of sedation as compared to other critically ill patients.¹² Although we did not include the question of the need for the use of second-line agents, many studies have reported the need for other agents for optimal sedation. Anton-Martin P et al. reported that about one-third of the children on ECMO required second-line agents.¹⁵ Altogether, these findings of the survey highlight the need and difficulty in achieving adequate sedation and the need for a higher dose or second-line agents or NMBAs for optimal sedation in children on ECMO. However, the adverse consequences of these drugs cannot be ignored and children on ECMO are at risk of these consequences.^9,19

We observed that nearly half of the respondents have and follow a protocolized sedation strategy. Although there has been no conclusive evidence on the utility of protocolized sedation in critically ill children, it is being followed with the assumption that having and adhering to a protocol may improve the outcomes in critically ill children.²⁰ Of the respondents, two-third reported they never practice awake ECMO in children and another one-third reported it is done in only <25% of children. This might be due to the obvious reasons for the risk of cannula malposition, bleeding, or decannulation. Although not widely used, there is increasing interest in the practice of awake ECMO in children with good success.^21,22 With various adverse consequences of sedatives and NMBAs, the practice of awake ECMO needs to be considered where feasible. However, the practice of awake ECMO in children is difficult and may be done in high-volume centers with good experience.

Critically ill children requiring sedation and analgesia are at higher risk for sedation withdrawal with frequency ranging from 7.5 to 100%.²³ Limited studies reported sedation withdrawal in children on ECMO. Schneider JB et al. observed that children requiring ECMO had higher sedation withdrawal as compared to children who did not require ECMO (27 vs 10%). In this survey, there was a mixed response with about 37% of respondents noting sedation withdrawal in <25% of children and about 20% noting sedation withdrawal in almost all children.

We observed that nearly 80% of the respondents felt that SRAEs affect the outcomes including duration of ventilation or PICU stay or hospital stay and 40% of them noted such an effect in about 25–50% of patients. Anton-Martin P et al., in their retrospective study, observed that higher doses of opiates and benzodiazepines were associated with prolonged ECMO runs, duration of ventilation, and PICU stay.

CONCLUSION

In this survey, we observed that a combination of benzodiazepines and opioids was the preferred agent with increasing use of dexmedetomidine as a first-line agent in children on ECMO. A greater proportion of children on ECMO have difficulty in achieving optimal sedation and need for higher doses or NMBAs. There is limited experience with awake ECMO in children in the Indian scenario. Sedation-related adverse events affect the duration of PICU and hospital stay. Future studies should focus on reporting sedation practices, effects on outcomes, and methods to improve outcomes related to sedation in children on ECMO.

ORCID

Kiran K Banothu https://orcid.org/0000-0001-6789-1109

Priyanka Gupta https://orcid.org/0000-0002-0373-8954

Anil Sachdev https://orcid.org/0000-0002-7624-6985

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