Choice and adequacy of sedation in critically ill mechanically ventilated children: A single center prospective observational study

Meenu Jose; Ardra Prakash; Neetu Gupta; Swathy Subhash; C Shijukumar; Prameela Joji

doi:10.4103/jpcc.jpcc_61_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 10 | Issue : 1 | Page : 30-35

Choice and adequacy of sedation in critically ill mechanically ventilated children: A single center prospective observational study

Meenu Jose, Ardra Prakash, Neetu Gupta, Swathy Subhash, C Shijukumar, Prameela Joji
Department of Pediatrics, KIMSHEALTH, Thiruvananthapuram, Kerala, India

Date of Submission	06-Jul-2022
Date of Decision	11-Nov-2022
Date of Acceptance	12-Dec-2022
Date of Web Publication	20-Jan-2023

Correspondence Address:
Dr. Meenu Jose
Malaikudiyil House, Kuruppampady P. O., Perumbavoor, Ernakulam - 683 545, Kerala
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcc.jpcc_61_22

Abstract

Background: Sedation management is a crucial element of pediatric critical care medicine, aiming at reducing children's anxiety, distress, and oxygen demand. Prolonged administration of sedatives may result in drug tolerance and physical dependency. Abrupt discontinuation of these drugs in children may cause withdrawal symptoms. Our study aims to evaluate the choice and adequacy of sedation in ventilated children using the University of Michigan Sedation Scale score.
Subjects and Methods: All the children aged between 1 and 12 years who were subjected to invasive ventilation during the time period October 2019 to June 2021 in the tertiary care pediatric intensive care unit (PICU) were included in the study.
Results: Of the 35 children enrolled in the study, most of them spend the majority of their time in adequate sedation which accounts for around 87.1% of the total time of ventilation. Fentanyl and midazolam were the most frequently used drug combination. Oversedation and undersedation accounted for 7.9% and 5% of total ventilation hours, respectively. Out of 35 children, 10 (28%) developed iatrogenic withdrawal symptoms and 4 (11%) developed severe withdrawal symptoms.
Conclusions: Fentanyl and midazolam were the most frequently used drug combination for attaining adequate sedation in our PICU. Irrespective of adequate sedation, no increase in the incidence of iatrogenic withdrawal syndrome, undersedation, or oversedation was noted in our study population.

Keywords: Analgesics, fentanyl, Pediatric risk of mortality score (PRISM III), sedatives, University of Michigan Sedation Scale, Withdrawal Assessment Tool-1

How to cite this article:
Jose M, Prakash A, Gupta N, Subhash S, Shijukumar C, Joji P. Choice and adequacy of sedation in critically ill mechanically ventilated children: A single center prospective observational study. J Pediatr Crit Care 2023;10:30-5

How to cite this URL:
Jose M, Prakash A, Gupta N, Subhash S, Shijukumar C, Joji P. Choice and adequacy of sedation in critically ill mechanically ventilated children: A single center prospective observational study. J Pediatr Crit Care [serial online] 2023 [cited 2023 Mar 25];10:30-5. Available from: http://www.jpcc.org.in/text.asp?2023/10/1/30/368233

Introduction

Sedation management is a crucial element of pediatric critical care medicine, aiming at reducing children's anxiety, distress, and oxygen demand.^[1] Adequate sedation has been described as the level of sedation at which patients are asleep but easily arousable. In pediatric intensive care unit (PICU) practice, this means that a child is conscious, breathing in synergy with the ventilator, and is tolerant to other therapeutic procedures. To achieve the optimal level of sedation in patients, the dose of sedatives is titrated to the effect based on observational sedation scales validated for the population in question. Both under and oversedation are undesirable, as these conditions may adversely affect patient outcomes.^[2]

In PICU, benzodiazepines and opioids are frequently used agents.^[2] Prolonged administration of sedatives may result in drug tolerance and physical dependency. Abrupt discontinuation or too rapid weaning of these drugs in children may cause iatrogenic withdrawal symptoms.^[2]

Different PICUs use a variety of combinations of sedatives and analgesia but the ideal choice of sedatives, depth, and duration of sedation to have a ventilation synergy without increasing the adverse effect such as iatrogenic withdrawal symptoms, myopathy, and prolonged ventilation have not been published so far. Less is known about the sedation practices and the clinical outcomes in a mechanically ventilated child in a tertiary care PICU, especially in an Indian setup. To fill up these lacunae, the current study was undertaken. The adequacy of sedation is commonly used sedatives and analgesics and the presence of iatrogenic withdrawal symptoms was also studied.

Materials and Methods

This prospective, observational study was conducted in a five-bedded PICU of a tertiary care hospital with an average of 10–15 admissions per month over 20 months (October 2019–June 2021) involving children aged 1–12 years who were on invasive ventilation for more than 24 h. Children presented with unexplained coma, psychiatric illness, a neurodegenerative disorder, and global developmental delay were excluded. The study was approved by the institute ethics committee (No KIMS/IHEC/FM06/2019) and parental consent was obtained before enrolment. The sample size was taken according to the census sampling method (all ventilated children during the study period who met the inclusion criteria).

The severity of illness was assessed using the PRISM III score by the resident doctor on duty. Total hours of invasive ventilation were calculated from the daily PICU monitoring chart and recorded in the study pro forma. The choice of sedatives and analgesics was decided as per disease condition and unit protocol. From this, aggregate hours of adequate sedation were obtained using the University of Michigan Sedation Scale (UMSS score of 1–3). The percentage time of adequate sedation, undersedation as well as oversedation was also calculated.

The primary outcome was the percentage of time that children spend in adequate sedation (UMSS score 1–3). Secondary outcomes studied were the most frequently used sedatives and analgesics in ventilated children, adequacy of sedation based on the severity of illness with respect to PRISM III score, and adequacy of sedation based on drugs used [Figure 1]. The presence of withdrawal symptoms (using the Withdrawal Assessment Tool-1 [WAT] every twelve-hourly after 72 h of intubation) if any in the study group was also recorded. WAT-1 score >3 indicates severe withdrawal. Diagnosis and clinical outcomes of all enrolled patients were recorded in the study pro forma from electronic medical records.

Figure 1: Study flow diagram

Click here to view

Data collected was tabulated using MS Excel and was analyzed using SPSS Statistics for Windows, version 16.0 (SPSS Inc., Chicago, III., USA). Results on categorical measurements were presented in numbers (%) and results on continuous measurements were presented in mean and standard deviation. The association between the severity of illness and adequacy of sedation was analyzed by analysis of variance(ANOVA) test. Association between continuous variables was analyzed using Student's t-test. A P < 0.05 was considered statistically significant

Results

Since the study was conducted during the period of the COVID-19 pandemic, the number of admissions to the PICU was significantly less. Forty-five children were ventilated during the study period, but eight were excluded as they were ventilated for <24 h. Thirty-seven children who received sedation for invasive ventilation during the study period were enrolled for the study, out of which two were excluded (cause for exclusion: refusal of consent – 1 and global developmental delay – 1). The most common age group enrolled was in between 1 and 6 years which constituted around 60% of the study population. The majority of children were male (85.7%) in our study [Table 1]. Central nervous system etiology constituted the most common cause for intubating the children followed by polytrauma and respiratory causes [Table 2].

Table 1: Baseline characteristics of the study

Click here to view

Table 2: Description of primary illness for which the child was ventilated and received sedation

Click here to view

The primary outcome measured was the percentage time that children spend in adequate sedation assessed in terms of UMSS.

Children who were ventilated and received sedatives and analgesics spent the majority of their time in adequate sedation which accounts for around 87.1% of the total time of ventilation. Oversedation and undersedation accounted for 7.9% and 5% of total ventilation hours, respectively [Table 3].

Table 3: Adequacy of sedation (percentage time spent on the University of Michigan Sedation Scale score 1-3)

Click here to view

Adequate sedation is denoted by red and its shades. The darker the red color, the more time the child had spent in adequate sedation. The bar diagram inside the red background shows the actual percentage of time the child had spent in adequate sedation. Undersedation and oversedation were represented by the gradients of green and yellow colors, respectively. Dark green shades indicate that the children spend less time, whereas yellow shades show that they spend more time in both under and oversedation [Figure 2].

Figure 2: Heat map showing the percentage time of adequate and under and oversedation of enrolled children

Click here to view

Secondary outcomes measured were the most frequently used sedatives and analgesics in ventilated children, adequacy of sedation based on the severity of illness with respect to PRISM III score, and to compare the adequacy of sedation based on drugs used. Fentanyl and midazolam were the most frequently used drug combination for attaining adequate sedation in ventilated children, that is 17 out of 35 (48.5%). Other agents used were as follows fentanyl alone, fentanyl-midazolam-ketamine, and fentanyl-midazolam-atracurium. Children spend most of the time in adequate sedation irrespective of the severity of illness. Undersedation (6.6%) was more likely when the severity of illness was mild and children with severe illness had a higher chance of oversedation (P = 0.8). Percentage time of undersedation (9.9%) tended to be more in children who were ventilated for respiratory etiology compared to other causes (P = 0.3), whereas oversedation was frequently seen in children with a history of polytrauma (15.3%, P = 0.6)

Children who received both protocols – fentanyl and midazolam/fentanyl alone for sedation were adequately sedated most of the time. Adequate sedation hours were similar in both groups (P = 0.5).

We also studied the occurrence of iatrogenic withdrawal symptoms in these ventilated children. Out of 35 children, 10 developed iatrogenic withdrawal symptoms after discontinuation of sedatives and analgesics. While comparing with those who did not develop withdrawal symptoms, the percentage time of oversedation was more in children with withdrawal symptoms, but it was not statistically significant (P = 0.38). In our study, four children out of 35 children developed severe withdrawal symptoms (WAT score >3). [Table 4] describes the clinical profile of children with severe withdrawal symptoms. The percentage time of oversedation was more in these children compared to other children who did not have withdrawal symptoms, even though it was statistically not significant (P = 0.3).

Table 4: Clinical profile of children with severe withdrawal symptoms (withdrawal assessment tool score >3): n=4

Click here to view

Discussion

Sedation is an essential part of the management of a critically ill child, and its monitoring must be individualized and continuous to adjust drug doses according to the clinical state. Effective sedation can facilitate mechanical ventilation, reduce anxiety, and allow for better tolerance of medical procedures. Oversedation delays recovery, as greater sedative consumption is associated with a longer duration of ventilation as well as extubation failure. It also induces tolerance and withdrawal syndrome. Undersedation, on the other hand, may lead to increased distress and adverse events such as unintentional extubation or displacement of catheters. All this may also lead to a longer intensive care unit stay.

Adequate sedation was achieved in 2433 h out of 2793 study hours in index study, accounting for 87.1% of total hours of ventilation. A study was done by Lopez et al.^[3] also had similar observations of achievement of adequate sedation in 837 h out of 1022 (81.9%) study hours. In the study done by Hayden et al.,^[4] optimal sedation was attained in 69% of the total study duration and was monitored with the help COMFORT behavior score. Another study by Playfor et al.^[5] assessed sedation using a 5 point Likert scale. Eighty-one assessments were carried out, of these 64 assessments (90%) were ideal as the sedation score correlated exactly with the desired level of sedation.

In our study, undersedation and oversedation occurred 140/2793 (5%) hours and 220/2793 (7.9%) hours, respectively. The study was done by Hayden et al.^[4] showed the percentage time of undersedation was 11% and that of oversedation was 16%. However, in the study by Arena Lopez et al.,^[3] the percentage time of undersedation was more (10.8%) compared to oversedation (7.8%). The majority of studies showed the incidence of oversedation is more common than undersedation in PICU. There are several reasons for the relatively high incidence of oversedation as there may be a tendency to avoid undersedation as this can lead to discomfort and potential adverse effects such as self-extubation and removal of intravenous lines and catheters.

We used midazolam-fentanyl combination in the majority of children (17/35, 48.5%). In the study done by Playfor et al.,^[5] they used a regimen of continuous intravenous midazolam and morphine for attaining adequate sedation. The drug of the first choice for sedation in the study done by Ista et al.^[6] was midazolam and when sedation is considered insufficient, they added morphine, ketamine, or fentanyl. Hayden et al.^[4] also used continuous infusions of opioids coadministered with benzodiazepines such as midazolam. The most commonly used drugs were midazolam for sedation and fentanyl for analgesia, and their combination is the most frequent in Argentine PICUs as shown by the study done by Taffarel et al.^[7]

We also assessed the association between the PRISM III score and adequacy of sedation. Children spend most of the time in adequate sedation irrespective of the severity of illness. There were no studies which evaluated the association between PRISM III score and adequacy of sedation.

Adequate sedation hours were similar in children who received both protocols – fentanyl and midazolam/fentanyl alone. Richman et al.^[8] done a study on 30 adult patients with respiratory failure who were on more than 48 h of mechanical ventilation. They received an intravenous infusion of either midazolam alone or midazolam with fentanyl. Ramsay score was used to assess the adequacy of sedation in this study. They found that compared with the midazolam-only group, the co-sedation group had fewer hours per day with an "off-target" Ramsay score.

Ista et al.^[9] done a study in the PICU of the Netherlands and had an incidence of withdrawal symptoms in 74 children out of 154 (48%). In the study done by Franck et al.,^[10] 21 children had withdrawal symptoms out of 126 (17%). They also used the WAT-1 score for assessing withdrawal symptoms. Rordriguez-Otero et al.^[11] done a study on risk factors of Opioid/Benzodiazepine-induced Withdrawal Syndrome in Critically Ill Hispanic Children and an incidence of 60% of Opioid/Benzodiazepine Iatrogenic Withdrawal Syndrome (IWS) was observed, with 50% of patients showing withdrawal signs within the first 14 days of admission. They found that younger patients (median: 24 months) and females (58%) were more prone to develop IWS.

da Silva et al.^[12] had done a prospective observational study and included a total of 137 patients who received a continuous infusion of fentanyl and midazolam for 3 or more days. The Sophia Observation Withdrawal Symptoms scale was used for assessing withdrawal symptoms. The overall incidence of IWS was 22.6%. Of the 31 IWS patients, six showed IWS with <5 days of sedation or analgesia. IWS can occur if these drugs are abruptly stopped or weaned too quickly in physically dependent children. Both longer duration of administration and high total doses of opioids and/or benzodiazepines are clearly related to the occurrence of a withdrawal syndrome in critically ill children.^[2]

Conclusions

Children who were ventilated and received sedatives and analgesics spent the majority of their time in adequate sedation. Fentanyl and midazolam were the most frequently used drug combination for attaining adequate sedation in ventilated children in our PICU. UMSS and WAT-1 scores are reliable to assess the adequacy of sedation and iatrogenic withdrawal symptoms, respectively.

Strengths of the study

This was one among the very few studies from India which has studied sedation, analgesic practices, and its clinical outcome in mechanically ventilated children. Our study indicates the importance of having a protocol for sedation and analgesia in invasively ventilated children to avoid both undersedation as well as oversedation. We used a well-validated scoring system for assessing sedation status as well as to monitor opioid and benzodiazepine withdrawal symptoms.

Limitations of the study

This was a single-center study and due to the small sample size cannot be generalized to the general population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Baarslag MA, Allegaert K, Knibbe CA, van Dijk M, Tibboel D. Pharmacological sedation management in the paediatric Intensive Care Unit. J Pharm Pharmacol 2017;69:498-513.
2.	Vet NJ, Kleiber N, Ista E, de Hoog M, de Wildt SN. Sedation in critically ill children with respiratory failure. Front Pediatr 2016;4:89.
3.	Arenas-López S, Riphagen S, Tibby SM, Durward A, Tomlin S, Davies G, et al. Use of oral clonidine for sedation in ventilated paediatric intensive care patients. Intensive Care Med 2004;30:1625-9.
4.	Hayden J, Dawkins I, Breatnach C, Foxton J, Healy M, Gallagher P, et al. A descriptive observational study of sedation outcomes and practices in mechanically ventilated children in an Irish PICU to inform future sedative effectiveness research studies. Eur J Pediatr 2016;11:1640-1.
5.	Playfor SD, Thomas DA, Choonara I, Jarvis A. Quality of sedation during mechanical ventilation. Paediatr Anaesth 2000;10:195-9.
6.	Ista E, van Dijk M, Tibboel D, de Hoog M. Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT "behavior" scale. Pediatr Crit Care Med 2005;6:58-63.
7.	Taffarel P, Bonetto G, Jorro Barón F, Meregalli C. Sedation and analgesia in patients on mechanical ventilation in pediatric Intensive Care Units in Argentina. Arch Argent Pediatr 2018;116:e196-203.
8.	Richman PS, Baram D, Varela M, Glass PS. Sedation during mechanical ventilation: A trial of benzodiazepine and opiate in combination. Crit Care Med 2006;34:1395-401.
9.	Ista E, de Hoog M, Tibboel D, Duivenvoorden HJ, van Dijk M. Psychometric evaluation of the Sophia Observation withdrawal symptoms scale in critically ill children. Pediatr Crit Care Med 2013;14:761-9.
10.	Franck LS, Scoppettuolo LA, Wypij D, Curley MA. Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain 2012;153:142-8.
11.	Rordriguez-Otero K, Puig-Ramos A, López-Ortiz CO, Pabon-Rivera S, Gomez M, Rodriguez K, et al. Risk factors of opioid/benzodiazepines-induced withdrawal syndrome in critically ill Hispanic children. Pediatrics 2018;141:329.
12.	da Silva PS, Reis ME, Fonseca TS, Fonseca MC. Opioid and benzodiazepine withdrawal syndrome in PICU patients: Which risk factors matter? J Addict Med 2016;10:110-6.