Sedation Management Research Articles

Abstract 13282: Towards a Decision Support Tool for Opioid Administration and Sedation Management in the Pediatric Cardiac Intensive Care Unit

Introduction: Opioids are commonly used to treat pain and agitation in the cardiac intensive care unit. However, responsiveness to opioids in pediatric patients is poorly understood, and few guidelines exist for personalized management of sedation. This leads to probable overprescription of opioids in the pediatric ICU, which can extend length of stay and have negative long-term health consequences. In this work, we build a decision support tool to predict a patient’s response to an opioid bolus measured by the state behavior scale (SBS), using available patient data at the time of administration. Methods: We built a dataset including all individual doses of morphine administered to patients admitted to the CICU between 2011-2020. Patients missing critical hemodynamic or SBS data were excluded from the analysis. The change in SBS score before and after morphine administration was converted to a binary outcome, where a decrease in SBS score was considered to be favorable (A). A LASSO regression model was trained to predict SBS response. The predictors utilized in the model included demographics, hemodynamic data, SBS score measurements before morphine, concomitant drug infusions/boluses and morphine response to prior doses. The model was trained on 80% of data and evaluated on 20%. Results: Of 197,242 intravenous boluses, 66,195 boluses administered to 6,021 patients (median age 7.2 mo) were included. The median change in SBS score was 0 (IQR -1 - 0) with 33% of administrations classified as favorable responses. The model coefficients are shown in (B). The model predicts 74% of unfavorable morphine responses with 95% confidence, AUC = 0.899 (C). Conclusions: Nearly three-quarters of ineffective responses to morphine can be predicted with 95% confidence using the prediction models developed. Such models could substantially reduce morphine over-administration for critically ill patients in the pediatric cardiac ICU.

Nonconvulsive status epilepticus following cardiac arrest—are we missing the beginning?

Abstract Background Status epilepticus (SE) is a common complication in patients surviving a cardiac arrest, but little is known about the frequency of nonconvulsive status epilepticus (NCSE). Objectives To compile the first the evidence from the literature of the overall frequency of NCSE in adults with persistent coma following cardiac arrest. Secondarily, to assess the emergence of NCSE in comatose resuscitated patients within the first hours of the return of spontaneous circulation (ROSC) and before inducing target temperature management. Material and methods The medical search engine PubMed was screened to identify prospective and retrospective studies in English reporting on the frequency of NCSE in comatose post-resuscitated patients. Study design, time of EEG performance, detection of SE and NCSE, outcomes, and targeted temperature management were assessed. Results Only three cohort studies (one prospective and two retrospective) reported on the EEG evaluation describing NCSE during ongoing sedation and target temperature management. Overall, we identified 213 patients with SE in 18–38% and NCSE in 5–12%. Our review found no study reporting NCSE in resuscitated adult patients remaining in coma within the first hours of ROSC and prior to targeted temperature management and sedation. Conclusion Studies of NCSE after ROSC in adults are rare and mostly nonsystematic. This and the low proportion of patients reported having NCSE following ROSC suggest that NCSE before target temperature management and sedation is often overlooked. The limited quality of the data does not allow firm conclusions to be drawn regarding the effects of NCSE on outcome calling for further investigations. Clinicians should suspect NCSE in patients with persistent coma before starting sedation and targeted temperature management.

Protocolized nurse-guided intravenous conscious sedation for cryoballoon ablation of paroxysmal and persistent atrial fibrillation

Abstract Background Nursing staff is playing an increasingly important role in arrhythmia units and it entails acquiring more specialized knowledge. Intravenous conscious sedation is being administered more frequently in a wide variety of cardiac procedures including cryoballoon ablation (CBA). Nurses and physicians have distinct yet collaborative roles in the management and care of the patient receiving conscious sedation. It is imperative that the nurse be aware of her/his role in caring for the patient before, during, and after the administration of intravenous conscious sedation. Purpose We aimed to evaluate the nurse's role, working in coordination with the medical staff, in intravenous conscious sedation for CBA following a standardized protocol ensuring proper handling and administration of the different drugs, monitorization of vital signs and management of drug infusion in order to avoid pain but also complications inherent to the procedure and sedation. Method We included consecutive patients with paroxysmal or persistent AF who underwent a CBA from 2017 to 2021. We evaluated a nurse-guided sedation, under medical surveillance, in CBA procedures using propofol. The dosage was based on the patient's weight, starting sedation with a bolus of 1 ml (1% solution) for every 20 kg of weight, and starting a perfusion at 10 ml/h (2% solution), monitoring constantly patient's vital signs, especially blood pressure and O2saturation. This infusion was adjusted according to the patient's response. During the procedure, on a stable hemodynamic situation, booster bolus of 1 ml (1% solution) could be administered approximately every 15 minutes when needed for sedation. When systolic blood pressure was under 100 mmHg, a solution of midazolam (1mg/ml) and fentanyl (0.05mg/ml) in a mixture of 1cc + 1cc was preferred as booster. Saline and colloid solutions andephedrine (30mg/ml) bolus could be used when severe hypotension to revert propofol's hypotensive effect. Systematic standardized CBA was performed and intraprocedural and periprocedural complications were recorded. Results 104 patients were included (mean age 58±8 year-old, 85% male). Of these patients, 76 (73%) had recurrent paroxysmal AF, failure of antiarrhythmic drugs was present in 96% and prior radiofrequency ablation in 4%, 61 (59%) showed left atria enlargement (>40 mm or area >20 cm2), and 11 (10%) had structural heart disease. Mean CHA2DS2VASc score was 1. Baseline characteristics in Table 1. Procedural-related complications occurred in 6 patients (5%), transient phrenic nerve palsy in 2 patients and vascular damage in 4. All sedations were performed without complications. Conclusions In our experience, protocolized nurse-guided intravenous conscious sedation under medical surveillance in CBA procedures is safe and really useful. It contributes to help medical operators to focus on the procedure sharing the patient's sedation management with trained nurses. Funding Acknowledgement Type of funding sources: None.

Bleeding Hazard of Percutaneous Tracheostomy in COVID-19 Patients Supported With Venovenous Extracorporeal Membrane Oxygenation: A Case Series

ObjectivesTracheostomy is usually performed to aid weaning from mechanical ventilation and facilitate rehabilitation and secretion clearance. Little is known about the safety of percutaneous tracheostomy in patients with severe COVID-19 supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO). This study aims to investigate the bleeding risk of bedside percutaneous tracheostomy in patients with COVID-19 infection supported with VV-ECMO.DesignA Retrospective review of electronic data for routine care of patients on ECMO.SettingTertiary, university affiliated national ECMO centre.ParticipantsCOVID-19 patients who underwent percutaneous tracheostomy while on VV-ECMO support.InterventionsNo intervention was conducted during this study. Measurements and Main Results: Electronic medical records of 16 confirmed COVID-19 patients who underwent percutaneous tracheostomy while on VV-ECMO support, including patient demographics, severity of illness, clinical variables, procedural complications, and outcome were compared with 16 non-COVID-19 cases. SPSS statistical software was used for statistical analysis. Demographic data were compared using the chi-square test and normality assumption was test using Shapiro-Wilk test. The indications for tracheostomy in all the cases were prolonged mechanical ventilation and sedation management. None of the patients suffered a life-threatening procedural complication within 48 hours. Moderate to severe bleeding was similar in both groups. There was no difference in 30 and 90-days mortality between both groups. As per routine screening results, none of the staff involved contracted COVID-19 infection.ConclusionsIn this case series percutaneous tracheostomy during VV-ECMO in COVID-19 patients appeared to be safe and did not pose additional risks to patients or healthcare workers.

Analgesia-based Sedation for Oral Surgery in Patients With Chronic Respiratory Obstructive Disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for postoperative cardiovascular and respiratory complications. Thus, intravenous sedation can be a better option than general anesthesia for surgery in patients with severe COPD. Herein, we present 2 cases of analgesia-based sedation in patients with severe COPD who underwent oral surgery. The current study aimed to discuss these cases to provide knowledge about the appropriate sedation management in patients with this disease. In the current cases, the patients received sufficient analgesia and minimum sedation (analgesia-based sedation). Moreover, dexmedetomidine was used for maintaining sedation and fentanyl for analgesic effects. Furthermore, we focused on providing the maximum analgesic effect of local anesthesia. The patients' vital signs were stable. They did not have any psychological or physical complaints, such as anxiety and pain, during the procedure. Then, they were discharged from the hospital without any complications. Thus, analgesia-based sedation can be an alternative option for oral surgery in patients with COPD.

The signaling and selectivity of α-adrenoceptor agonists for the human α2A, α2B and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors.

α2‐adrenoceptors, (α2A, α2B and α2C‐subtypes), are Gi‐coupled receptors. Central activation of brain α2A and α2C‐adrenoceptors is the main site for α2‐agonist mediated clinical responses in hypertension, ADHD, muscle spasm and ITU management of sedation, reduction in opiate requirements, nausea and delirium. However, despite having the same Gi‐potency in functional assays, some α2‐agonists also stimulate Gs‐responses whilst others do not. This was investigated. Agonist responses to 49 different α‐agonists were studied (CRE‐gene transcription, cAMP, ERK1/2‐phosphorylation and binding affinity) in CHO cells stably expressing the human α2A, α2B or α2C‐adrenoceptor, enabling ligand intrinsic efficacy to be determined (binding KD/Gi‐IC50). Ligands with high intrinsic efficacy (e.g., brimonidine and moxonidine at α2A) stimulated biphasic (Gi‐Gs) concentration responses, however for ligands with low intrinsic efficacy (e.g., naphazoline), responses were monophasic (Gi‐only). ERK1/2‐phosphorylation responses appeared to be Gi‐mediated. For Gs‐mediated responses to be observed, both a system with high receptor reserve and high agonist intrinsic efficacy were required. From the Gi‐mediated efficacy ratio, the degree of Gs‐coupling could be predicted. The clinical relevance and precise receptor conformational changes that occur, given the structural diversity of compounds with high intrinsic efficacy, remains to be determined. Comparison with α1 and β1/β2‐adrenoceptors demonstrated subclass affinity selectivity for some compounds (e.g., α2:dexmedetomidine, α1:A61603) whilst e.g., oxymetazoline had high affinity for both α2A and α1A‐subtypes, compared to all others. Some compounds had subclass selectivity due to selective intrinsic efficacy (e.g., α2:brimonidine, α1:methoxamine/etilefrine). A detailed knowledge of these agonist characteristics is vital for improving computer‐based deep‐learning and drug design.

Delirium-assessment, prevention and treatment : Task in the interprofessional intensive care unit team

Postoperative delirium is achallenge for patients, relatives, nurses, physicians, and healthcare systems. Delirium is associated with increased mortality, longer hospitalization, reduced quality of life, and higher average treatment costs. Consequently, the most recent version of the German Guideline on Analgesia, Sedation and Delirium Management in Intensive Care Medicine (DAS Guideline 2020) emphasizes the importance of delirium prevention. In particular, nonpharmacological interventions play a special role in this regard for basically all patients receiving intensive care. The DAS Guideline stresses the importance of regular systematic screening with validated instruments to recognize developing delirium early and take the appropriate measures in time, as the duration of delirious conditions influences both mortality and quality of life. If delirium manifests, intervention must be immediate and symptom-oriented.

Evolution of sedation management in the intensive care unit (ICU).

Evolution of sedation management in the intensive care unit (ICU).

Pediatric Critical Care Nursing Research Priorities in Asia: An eDelphi Study.

To identify nursing research priorities in pediatric critical care in Asia. We conducted a modified three-round eDelphi survey with pediatric critical care nurses in Asia. The eDelphi technique has been extensively used within health research to achieve a common viewpoint from experts using questionnaires to gather research priorities. In round 1, participants were asked to list three to five research topics that they deemed important. These topics were thematically analyzed and categorized into a questionnaire. Participants rated the research topics in round 2 on a 6-point scale (1 = not important to 6 = extremely important). In round 3, the same questionnaire was used with addition of the calculated mean scores from round 2 for each topic. Research topics ranked among the top 10 were considered extremely important. Twenty-two PICUs in eight Asian countries. Clinical nurses, managers, educators, and researchers. None. In round 1, 146 PICU nurses across eight countries provided 520 research topics. Topics from round 1 were categorized into seven domains with 52 research topics. Prioritized research topics included early recognition of patient deterioration (mean 5.58 ± 0.61), prevention of healthcare-associated infections (mean 5.47 ± 0.70), and interventions to reduce compassion fatigue (mean 5.45 ± 0.80). The top three research domains were end-of-life care (mean 5.34 ± 0.68), professionalism (mean 5.34 ± 0.69), and management of pain, sedation, and delirium (5.32 ± 0.72). This first PICU nursing research prioritization exercise within Asia identified key nursing research themes that should be prioritized and provide a framework for future collaborative studies.

The Application of the Nurse-Led Sedation and Analgesia Management in ICU after Heart Surgeries.

Aim Traditional sedation management consists of doctors adjusting the dosage of sedative drugs or adding other drugs in combination according to the evaluation of nurses; the nurses then execute the orders. The nurses' passive execution in the process is not the ideal model for continuous evaluation and observation of sedation. This study aims to investigate the application and effects of nurse-provided procedural sedation and analgesia for patients in intensive care unit. Methods The experimental group consisted of 354 heart surgery patients who received procedural sedation and analgesia from nurses from November 2020 to August 2021. The control group consisted of 301 patients who had had heart surgery and received the traditional sedation management program from January to October 2020. The differences in levels of the sedative effect, delirium, and unplanned extubation of patients between these two groups were compared. Results There were no significant differences in baseline characteristics between the two groups (P > 0.05). It was found that both insufficient sedation and excessive sedation decreased in the experimental group when compared to the control group, while the appropriate proportion of sedation increased (72.41% versus 37.98%); the difference was statistically significant (P < 0.05). The incidence of delirium was lower for patients in the experimental group than for patients in the control group (37.01% versus 66.45%); the difference was statistically significant (P < 0.05). The incidence of unplanned extubation caused by patient factors was lower for the experimental group than for the control group, but the difference was not statistically significant (P > 0.05). Conclusion The programmed sedation scheme led by nurses can improve the sedation effect and reduce the incidence of delirium. Implications for Practice. The management team gives the sedative goal and establishes the standard flowchart. The sedation management led by the nurse according to the goal and flowchart is better than the traditional sedation management.

Implementation Science in Pediatric Critical Care - Sedation and Analgesia Practices as a Case Study.

Sedation and analgesia (SA) management is essential practice in the pediatric intensive care unit (PICU). Over the past decade, there has been significant interest in optimal SA management strategy, due to reports of the adverse effects of SA medications and their relationship to ICU delirium. We reviewed 13 studies examining SA practices in the PICU over the past decade for the purposes of reporting the study design, outcomes of interest, SA protocols used, strategies for implementation, and the patient-centered outcomes. We highlighted the paucity of evidence-base for these practices and also described the existing gaps in the intersection of implementation science (IS) and SA protocols in the PICU. Future studies would benefit from a focus on effective implementation strategies to introduce and sustain evidence-based SA protocols, as well as novel quasi-experimental study designs that will help determine their impact on relevant clinical outcomes, such as the occurrence of ICU delirium. Adoption of the available evidence-based practices into routine care in the PICU remains challenging. Using SA practice as an example, we illustrated the need for a structured approach to the implementation science in pediatric critical care. Key components of the successful adoption of evidence-based best practice include the assessment of the local context, both resources and barriers, followed by a context-specific strategy for implementation and a focus on sustainability and integration of the practice into the permanent workflow.

Potential for nitrous oxide sedation in pedodontics practice to reduce the need for dental general anesthesia.

To investigate the possible reduction in the need for dental general anesthesia through nitrous oxide sedation in combination with behavior management techniques among patients younger than 12 years of age referred to a specialized pedodontics practice due to high dental treatment need and poor cooperation with dental treatments. Retrospective analysis of the digital medical records of all children treated under nitrous oxide sedation in a specialized pedodontics clinic between 2012 and 2017 was performed. The reduction of the need for dental general anesthesia was measured depending on the success rate of nitrous oxide sedation at the patient level with relation to multiple related factors such as age, reason for referral, and treatment need. Nitrous oxide was used in 406 dental treatment sessions on 228 pre-cooperative and/or anxious patients aged 3 to 12 years (mean 6.4 ± 1.7; 43.4% female); 91.9% of the nitrous oxide sedation sessions were successful in achieving the intended dental treatment. Complete oral rehabilitation was possible for 84.0% of the patients using nitrous oxide sedation without the need for dental general anesthesia. Regarding age, dental general anesthesia reduction among preschool children was lower than school children (77.8% and 87.9%, respectively). A high proportion of anxious or semi-cooperative children with high dental treatment need can be treated without the use of dental general anesthesia when a comprehensive concept of caries management is combined with the use of nitrous oxide sedation and behavior management techniques. Nitrous oxide sedation should therefore be considered as an option for dental treatment of semi-cooperative children with high dental treatment need before planning dental general anesthesia.

Dental Treatment under General Anesthesia in Patients with Special Needs Provided by Private and Public Healthcare Services-A Retrospective, Comparative Study.

In special care dentistry, general anesthesia (GA) is considered as an alternative option to facilitate treatment for uncooperative patients with special needs (PSN) who require invasive dental interventions. Objective: to evaluate the profile of dental treatment procedures performed and the characteristics of PSN who underwent dental treatment under GA, provided by private and public healthcare providers. Methods: A retrospective, observational study involving a sample of 100 PSN treated in hospital and specialist secondary care settings. Demographic data and clinical information were collected. The analysis of data was performed using descriptive analysis and frequency statistical tests. Results: out of 100 participants, 63% of the PSN who received care in the private sector and the remaining 37% of PSN registered with public-funded care providers, aged 6 to 80 years old, were treated under GA. Autistic spectrum disorder was the most common medical diagnosis recorded (33%). More than half (52%) of the PSN treated by private care providers sought specialist care in an outpatient setting prior to GA vs. 5% of the PSN treated by public-funded providers. The utilization of sedation prior to GA was more common in the private sector. A vast majority (86%) of all subjects underwent multiple dental extractions (86%) and restorations (62%). Conclusions: comprehensive dental care under GA, which composes an integral part of special care dentistry, can be safely provided in a hospital setting, in both private and public sectors. While early intervention using sedation and behavioral management partially mitigates the need for dental care under GA, the vast majority of PSN may require dental treatment under GA in future to facilitate complex dental care.

Electroencephalogram-Based Evaluation of Impaired Sedation in Patients with Moderate to Severe COVID-19 ARDS.

The sedation management of patients with severe COVID-19 is challenging. Processed electroencephalography (pEEG) has already been used for sedation management before COVID-19 in critical care, but its applicability in COVID-19 has not yet been investigated. We performed this prospective observational study to evaluate whether the patient sedation index (PSI) obtained via pEEG may adequately reflect sedation in ventilated COVID-19 patients. Statistical analysis was performed by linear regression analysis with mixed effects. We included data from 49 consecutive patients. None of the patients received neuromuscular blocking agents by the time of the measurement. The mean value of the PSI was 20 (±23). The suppression rate was determined to be 14% (±24%). A deep sedation equivalent to the Richmond Agitation and Sedation Scale of −3 to −4 (correlation expected PSI 25–50) in bedside examination was noted in 79.4% of the recordings. Linear regression analysis revealed a significant correlation between the sedative dosages of propofol, midazolam, clonidine, and sufentanil (p < 0.01) and the sedation index. Our results showed a distinct discrepancy between the RASS and the determined PSI. However, it remains unclear to what extent any discrepancy is due to the electrophysiological effects of neuroinflammation in terms of pEEG alteration, to the misinterpretation of spinal or vegetative reflexes during bedside evaluation, or to other causes.

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study

BackgroundMechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.Study design and methodsDual-center, retrospective cohort study conducted over 6 months (March–August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of − 3 to − 5 or Riker Sedation-Agitation Scale of 1–3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days.Results391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65–7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19.ConclusionsThe management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

Avoiding, Not Managing, Drug Withdrawal Syndrome in the Setting of COVID-19 Acute Respiratory Distress Syndrome. Comment on Ego et al. How to Manage Withdrawal of Sedation and Analgesia in Mechanically Ventilated COVID-19 Patients? J. Clin. Med. 2021, 10, 4917.

The management of sedation in the setting of COVID-19 ("COVID") by Ego et al. [...].

Monitoring of sedation in mechanically ventilated patients using remote technology.

Two years of coronavirus disease 2019 (COVID-19) pandemic highlighted that excessive sedation in the ICU leading to coma and other adverse outcomes remains pervasive. There is a need to improve monitoring and management of sedation in mechanically ventilated patients. Remote technologies that are based on automated analysis of electroencephalogram (EEG) could enhance standard care and alert clinicians real-time when severe EEG suppression or other abnormal brain states are detected. High rates of drug-induced coma as well as delirium were found in several large cohorts of mechanically ventilated patients with COVID-19 pneumonia. In patients with acute respiratory distress syndrome, high doses of sedatives comparable to general anesthesia have been commonly administered without defined EEG endpoints. Continuous limited-channel EEG can reveal pathologic brain states such as burst suppression, that cannot be diagnosed by neurological examination alone. Recent studies documented that machine learning-based analysis of continuous EEG signal is feasible and that this approach can identify burst suppression as well as delirium with high specificity. Preventing oversedation in the ICU remains a challenge. Continuous monitoring of EEG activity, automated EEG analysis, and generation of alerts to clinicians may reduce drug-induced coma and potentially improve patient outcomes.

Dilemas éticos de pediatras ao administrar sedação paliativa em crianças no Brasil

Abstract This study aims to analyze the use of pediatric palliative sedation and understand how it is connected to medical training and the doctor-patient relationship in Brazil. This is a cross-sectional exploratory study using an online survey targeted at pediatricians working in Brazil to evaluate concepts of palliative sedation and aggressive symptom management. The lack of specific training, protocols, and institutionalized guidelines can create uncertainties in palliative care. This also contributes to the increased end-of-life suffering those children and their families face. Improving education in pediatric palliative care is an urgent and pressing need in Brazil.

Use of dexmedetomidine in complex treatment of patients in intensive care units

Sedation is an important aspect of adequate treatment of patients in the intensive care unit. Recent drug developments and new ventilation strategies provide improved sedation management that allows for better adaptation to the clinical condition and individual needs of the patient. This article provides an overview of the general principles of sedation of patients in intensive care units and focuses on a relatively new drug in the pharmaceutical market of Ukraine — dexmedetomidine. Given the pandemic of coronavirus disease COVID-19, there was carried out a review of the international and domestic literature describing the use of dexmedetomidine as a sedative and analgesic in patients with acute respiratory distress syndrome caused by SARS-COV-2 virus. Its anti-inflammatory and antioxidant properties are also described, which will allow the use of the drug in complex therapy in the treatment of COVID-19 in severe patients.

Interventions for the management of Pain and Sedation in Newborns undergoing Therapeutic hypothermia for hypoxic-ischemic encephalopathy (IPSNUT): protocol of a systematic review

BackgroundClinical research has shown that therapeutic hypothermia after neonatal hypoxic-ischemic injury improves survival without disability. There is no consensus regarding pain relief or sedation during therapeutic hypothermia in newborns; however, therapeutic hypothermia seems to be associated with pain and stress, and adequate analgesia and sedation are central to maximize the effect of therapeutic hypothermia. Pain needs to be adequately managed in all patients, especially the newborn infant due to the potential short- and long-term negative effects of inadequately treated pain in this population.MethodsWe will perform a systematic review of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy. We will include randomized, quasi-randomized controlled trials and observational studies. The use of pharmacological or non-pharmacological interventions will be compared to other pharmacological and or non-pharmacological interventions or no intervention/placebo. The primary outcomes for this review will be analgesia and sedation assessed with validated pain scales, circulatory instability, mortality to discharge, and moderate-to-severe neurodevelopmental disability. We will search the following databases: CINAHL, ClinicalTrials.gov, Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Two independent researchers will screen the records for inclusion, extract data using a data extraction form, and assess the risk of bias in the included trials.DiscussionThe result of this review will summarize the knowledge regarding the management of pain and sedation in infants treated with therapeutic hypothermia and potentially provide clinicians with guidance on the effective and safe methods.Systematic review registrationPROSPERO CRD42020205755