Exploring the Possible Role of Cannabinoids in Managing Post-cardiac Surgery Complications: A Narrative Review of Preclinical Evidence and a Call for Future Research Directions.

ABSTRACT: Open-heart surgery with cardiopulmonary bypass often leads to complications including pain, systemic inflammation, and organ damage. Traditionally managed with opioids, these pain relief methods bring potential long-term risks, prompting the exploration of alternative treatments. The legalization of cannabis in various regions has reignited interest in cannabinoids, such as cannabidiol, known for their anti-inflammatory, analgesic, and neuroprotective properties. Historical and ongoing research acknowledges the endocannabinoid system's crucial role in managing physiological processes, suggesting that cannabinoids could offer therapeutic benefits in postsurgical recovery. Specifically, cannabidiol has shown promise in managing pain, moderating immune responses, and mitigating ischemia/reperfusion injury, underscoring its potential in postoperative care. However, the translation of these findings into clinical practice faces challenges, highlighting the need for extensive research to establish effective, safe cannabinoid-based therapies for patients undergoing open-heart surgery. This narrative review advocates for a balanced approach, considering both the therapeutic potential of cannabinoids and the complexities of their integration into clinical settings.

The Reviewer Academy of the Society of Critical Care Medicine: Key Principles and Strategic Plan.

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers.

Perioperative Care Models for Neonates With Congenital Heart Disease: Evolving Role of Neonatology Within the Cardiac Intensive Care Unit.

A multidisciplinary team is needed to optimally care for infants with congenital heart disease (CHD). Different compositions of teams trained in cardiology, critical care, cardiothoracic surgery, anesthesia, and neonatology have been identified as being primarily responsible for perioperative care of this high-risk population in dedicated cardiac intensive care units (CICUs). Although the specific role of cardiac intensivists has become more well defined over the past two decades, the responsibilities of neonatologists remain highly variable in the CICU with neonatologists providing care along with a unique spectrum of primary, shared, or consultative care. The neonatologist can function as the primary physician and assume all or share responsibility with the cardiac intensivists for the management of infants with CHD. A neonatologist can provide care as a secondary consultant physician in a supportive role for the primary CICU team. Additionally, neonates with CHD can be mixed with older children in a CICU, cohorted in a dedicated space within the CICU or placed in a stand-alone infant CICU without older children. Although variations exist between centers on which model of care is deployed and the location within a CICU, characterization of current practice patterns represents the initial step required to determine optimal best practices to improve the quality of care for neonates with cardiac disease. In this manuscript, we present four models utilized in the United States in which the neonatologist provides neonatal-cardiac-focused care in a dedicated CICU. We also outline the different permutations of location where neonates can be cared for in dedicated pediatric/infant CICUs.

Beyond Conventional Hemodynamic Monitoring-Monitoring to Improve Our Understanding of Disease Process and Interventions.

Monitoring the hemodynamic state of patients is a hallmark of any intensive care environment. However, no single monitoring strategy can provide all the necessary data to paint the entire picture of the state of a patient; each monitor has strengths and weaknesses, advantages, and limitations. We review the currently available hemodynamic monitors used in pediatric critical care units using a clinical scenario. This provides the reader with a construct to understand the progression from basic to more advanced monitoring modalities and how they serve to inform the practitioner at the bedside.

Comparison of Laboratory and Hemodynamic Time Series Data Across Original, Alpha, and Delta Variants in Patients With Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: To compare the clinical, laboratory, and hemodynamic parameters during hospitalization for patients with multisystem inflammatory syndrome in children (MIS-C), across the Original/Alpha and the Delta variants of severe acute respiratory syndrome coronavirus 2 infection. DESIGN: Retrospective cohort study. SETTING: Single-center quaternary children's hospital. PATIENTS: Children with MIS-C admitted from May 2020 to February 2021(Original and Alpha variant cohort) and August 2021 to November 2021 (Delta variant cohort). MEASUREMENTS AND MAIN RESULTS: Continuous vital sign measurements, laboratory results, medications data, and hospital outcomes from all subjects were evaluated. Of the 134 patients (102 with Original/Alpha and 32 with Delta), median age was 9 years, 75 (56%) were male, and 61 (46%) were Hispanics. The cohort with Original/Alpha variant had more males (61% vs 41%; p = 0.036) and more respiratory/musculoskeletal symptoms on presentation compared with the Delta variant ( p < 0.05). More patients in the Original/Alpha variant cohort received mechanical ventilation (16 vs 0; p = 0.009). Median hospital length of stay (LOS) was 7 days, and ICU LOS was 3 days for the entire cohort. ICU LOS was shorter in cohort with the Delta variant compared with the Original/Alpha variant (4 vs 2 d; p = 0.001). Only one patient had cardiac arrest, two needed extracorporeal membrane oxygenation, and two needed left ventricular assist device (Impella, Danvers, MA), all in the Original/Alpha variant cohort; no mortality occurred in the entire cohort. MIS-C cohort associated with the Delta variant had lower INR, prothrombin time, WBCs, sodium, phosphorus, and potassium median values ( p < 0.05) during hospitalization compared with the Original/Alpha variants. Hemodynamic assessment showed significant tachycardia in the Original/Alpha variants cohort compared with the Delta variant cohort ( p < 0.05). INTERVENTIONS: None. CONCLUSIONS: Patients with MIS-C associated with the Delta variants had lower severity during hospitalization compared with the Original/Alpha variant. Analysis of distinct trends in clinical and laboratory parameters with future variants of concerns will allow for potential modification of treatment protocol.

Opioid Weaning Protocol Using Morphine Compared With Nonprotocolized Methadone Associated With Decreased Dose and Duration of Opioid After Norwood Procedure.

OBJECTIVES: Opioids are used to manage pain, comfort, maintain devices, and decrease oxygen consumption around Norwood palliation (NP), but in high dose and prolonged exposure, they increase risk of tolerance and iatrogenic withdrawal syndrome (IAWS). Variability in practice for IAWS prevention potentially increases opioid dose and duration. We hypothesize that protocolized weaning with morphine (MOR) versus nonprotocolized methadone (MTD) is associated with reduction in opioid exposure. DESIGN: A before-versus-after study of outcomes of patients weaned with protocolized MOR versus nonprotocolized MTD including subset analysis for those patients with complications postoperatively. Primary endpoints include daily, wean phase, and total morphine milligram equivalent (MMEq) dose, duration, and, secondarily, length of stay (LOS). SETTING: Quaternary-care pediatric cardiac ICU. PATIENTS: Neonates undergoing single-ventricle palliation. INTERVENTIONS: Introduction of IAWS prevention protocol. MEASUREMENTS AND MAIN RESULTS: Analysis included 54 patients who underwent the NP in 2017-2018 including the subset analysis of 34 who had a complicated postoperative course. The total and wean phase opioid doses for the MTD group were significantly higher than that for the MOR group: 258 versus 22 and 115 versus 6 MMEq/kg; p < 0.001. Duration of opioid exposure was 63 days in the MTD group and 12 days in MOR group (p < 0.001). Subanalysis of the complicated subset also identifies higher total and wean dose for MTD group (293 vs 41 and 116 vs 7 MMEq/kg; p < 0.001) with a longer duration (65 vs 22 days; p = 0.001). Within the subset, LOS was 55% longer in the MTD group than that in the MOR group (150 vs 67 d; p = 0.01) and not different in the uncomplicated group. CONCLUSIONS: After complex NP, a protocolized opioid weaning using MOR versus MTD is associated with 65% shorter opioid duration, 10-fold decreased dose, and shortened LOS.

Hemodynamic Response to Calcium Chloride Boluses in Single-Ventricle Patients with Parallel Circulation.

The purpose of this study is to assess the effect of calcium bolus in response to a hypotensive episode by assessing high-fidelity hemodynamic data obtained from children with single-ventricle physiology with parallel circulation. Single-center, retrospective analysis of hemodynamic data after calcium bolus administrations within the first 2 weeks post-surgery. Time intervals were the baseline (- 60 to - 10 min); the hypotensive episode (- 10 to 0 min); time point zero at the bolus administration; and the response (0 to 60 min). The main responses assessed were the peak increase in mean blood pressure (mBP), duration of the response after the bolus, and markers of oximetric effects. These analyses included 128 boluses in 63 patients. Of the total boluses analyzed, 80% increased the mBP by 5 mmHg or higher with the effect lasting at least 10 min, whereas 10% of the boluses analyzed increased the mBP by 20 mmHg or higher with the effect lasting at least 50 min. The boluses induced a significant increase in arterial oxygen saturation and an upward trend in pulmonary-to-systemic flow ratio, without increasing renal or cerebral oxygen extraction ratios. Calcium chloride boluses are an effective rescue medication for hypotensive episodes in children with parallel circulation. They lead to an improvement in mBP, as well as an increase in pulmonary-to-systemic blood flow ratio. More importantly, these boluses do not compromise systemic oxygen delivery.

Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Cardiovascular dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE: We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION: Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member. RESULTS: Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition. LIMITATIONS: All included studies were observational and many were retrospective. CONCLUSIONS: The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction.

RBC Transfusion Induced ST Segment Variability Following the Norwood Procedure.

The transfusion of stored RBCs decreases nitric oxide bioavailability, which may have an adverse effect on vascular function. We assessed the effects of RBC transfusion on coronary vascular function by evaluating the relationship between myocardial oxygen delivery and demand as evidenced by ST segment variability. DESIGN: Retrospective case-control study. SETTING: Nine-hundred seventy-three-bed pediatric hospital with a 54-bed cardiovascular ICU. PATIENTS: Seventy-three neonates with hypoplastic left heart syndrome following the Norwood procedure, 38 with a Blalock-Taussig shunt and 35 with a right ventricle to pulmonary artery shunt. INTERVENTIONS: RBC transfusion. MATERIALS AND MAIN RESULTS: High-frequency physiologic data were captured 30 minutes prior to the initiation of (baseline) and during the 120 minutes of the transfusion. A rate pressure product was calculated for each subject and used as an indicator of myocardial oxygen demand. Electrocardiogram leads (aVL, V1, II) were used to construct a 3D ST segment vector to assess ST segment variability and functioned as a surrogate indicator of myocardial ischemia. One-hundred thirty-eight transfusions occurred in the Blalock-Taussig shunt group and 139 in the right ventricle to pulmonary artery shunt group. There was no significant change in the rate pressure product for either group; however, ST segment variability progressively increased for the entire cohort during the transfusion, becoming statistically significant by the end of the transfusion. Upon subgroup analysis, this finding was noted with statistical significance in the Blalock-Taussig shunt group and trending toward significance in the right ventricle to pulmonary artery shunt group. CONCLUSIONS: We found a significant increase in the ST segment variability and evidence of myocardial ischemia temporally associated with RBC transfusions in neonates following the Norwood procedure, specifically among those in the Blalock-Taussig shunt group, which may impact immediate and long-term outcomes.

Impact of Corticosteroids on Cardiopulmonary Bypass Induced Inflammation in Children: A Meta-Analysis.

BACKGROUND: Corticosteroids suppress the inflammatory response to cardiopulmonary bypass in children undergoing cardiac surgery. What is less clear is the impact of corticosteroids on the postoperative course. METHODS: A systematic review and meta-analysis was made of prospective randomized blinded placebo-controlled trials of pediatric patients who received corticosteroids or saline placebo before surgery was performed. Ten studies met inclusion criteria for a total of 768 patients. In a prespecified subgroup analysis, studies that either were limited to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery congenital heart surgery mortality categories 1 and 2 or excluded neonates were eliminated and a secondary analysis was conducted, which consisted of seven studies and 555 patients. RESULTS: Corticosteroids were associated with a significant improvement in fluid balance at 24 and 36 hours after surgery, with a mean difference of -15.2 mL/kg (95% confidence interval, 25.3 to -5.1 mL/kg; P < .01) and -5.7 mL/kg (95% confidence interval, -9.8 to -1.6 mL/kg; P < .01), respectively. Corticosteroids had no impact on the incidence of infection or mortality. With the secondary analysis, corticosteroids were associated with a trend toward significance in shortening the duration of mechanical ventilation (mean difference -0.7 days; 95% confidence interval, -1.7 to 0.1; P = .08). CONCLUSIONS: Corticosteroids were found to have a favorable impact on postoperative fluid balance and may be associated with shortening the duration of mechanical ventilation. Although corticosteroids had no impact on mortality, they may be beneficial particularly for neonates and patients undergoing highly complex surgery.

Xanthine Derivatives for Kidney Protection in the Critically Ill Pediatric Population: A Systematic Review.

Different types of diuretics have been used to minimize fluid overload after resuscitation. This meta-analysis determined the effects of xanthine derivatives on creatinine, creatinine clearance, and urine output. Studies included data from pediatric patients, whoused theophylline or aminophylline, and included pre- and postxanthine data for at least one of the outcomes of interest. A total of 13 studies with 198 patients were included in the pooled analyses. The study recorded data prior, and a mean of 36 hours after xanthine administration. This meta-analysis demonstrates that xanthine derivatives in critically ill children, using a dose of approximately5 mg/kg, lead to a statistically significant increase in creatinine clearance and urine output without significantly altering serum creatinine. Xanthine derivatives may be beneficial for fluid management in critically ill children. Further studies are warranted assessing the association with additional clinical outcomes.

Epidemiology and Outcomes of Acute Decompensated Heart Failure in Children.

BACKGROUND: Acute decompensated heart failure (ADHF) is a highly morbid condition among adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF. METHODS: Cardiac intensive care unit (CICU) patients ≤18 years of age meeting Pediatric Cardiac Critical Care Consortium criteria for ADHF were included. ADHF was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis, therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality were identified using logistic regression. RESULTS: Among 26 294 consecutive admissions (23 centers), 1494 (6%) met criteria for analysis. Median age was 0.93 years (interquartile range, 0.1-9.3 years). Patients with congenital heart disease (CHD) comprised 57% of the cohort. Common therapies included the following: vasoactive infusions (88%), central venous catheters (86%), mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%). Median length of CICU stay was 7.9 days (interquartile range, 3-18 days) and the CICU readmission rate was 22%. Overall, CICU mortality was 15% although higher for patients with CHD versus non-CHD (19% versus 11%; P<0.001). Independent risk factors associated with CICU mortality included age <30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary hypertension, extracorporeal membrane oxygenation, and cardiac arrest. CONCLUSIONS: ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with CHD. Opportunities exist to determine best practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal heart transplantation candidacy to improve outcomes for these patients.

SENTINEL1: Two-Season Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

OBJECTIVE: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons. STUDY DESIGN: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized. RESULTS: Results were similar across the two seasons. Among infants with community-acquired RSVH (N = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge. CONCLUSION: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV.

Thyroid Hormone (Triiodothyronine) Therapy in Children After Congenital Heart Surgery: A Meta-Analysis.

Thyroid hormone modifies metabolic, immune and cardiovascular functions and has been administered perioperatively to treat a relative reduction of thyroid function in children following cardiopulmonary bypass (CPB) for correction of congenital heart disease. However, it remains unclear whether its use is associated with improved outcomes. We performed a meta-analysis of studies that evaluated the impact of thyroid hormone supplementation on clinical outcomes in children undergoing repair of congenital heart disease using CPB. A systematic review of published trials was conducted to identify studies of children randomized to thyroid hormone supplementation or placebo undergoing congenital heart surgery. A meta-analysis was then conducted to determine the clinical impact of thyroid hormone replacement on cardiac function and postoperative characteristics. The following outcomes were included for the study: duration of mechanical ventilation, duration of intensive care unit (ICU) stay, duration of postoperative hospital stay, inotrope score, cardiac index at 24 hours postoperatively, and inpatient mortality. A total of 9 studies with 711 patients were included in the analyses. All included studies were prospective and patients were randomized to either thyroid hormone or placebo. There was wide variation in thyroid hormone dosing, ranging from 0.4 µg/kg up to 5 µg/kg over a 24-hour period, and duration of therapy, ranging from a single dose after cessation of CPB to continued thyroid hormone for the duration of the ICU stay. There was a significant difference in the mean inotrope score between the 2 groups of -1.249 (95% confidence interval -1.570 to -0.929, P < 0.001), with the inotrope score being significantly lower in the thyroid group. There was no difference in duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, cardiac index, and mortality between groups. In this meta-analysis, routine thyroid hormone replacement with approximately 1-5 µg/kg administered over 24 hours does not significantly alter the postoperative course in children following CPB. However, given a clinically small but significant difference in respect to lower inotrope score and shorter duration of ICU and hospital stays with higher thyroid replacement additional studies are warranted.