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.

Open-heart surgery with cardiopulmonary bypass (CPB) 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 CBD, 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 cannabinoids could offer therapeutic benefits in post-surgical recovery. Specifically, CBD 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.

Application of Cardiovascular Physiology to the Critically Ill Patient.

OBJECTIVES: To use the ventricular pressure-volume relationship and time-varying elastance model to provide a foundation for understanding cardiovascular physiology and pathophysiology, interpreting advanced hemodynamic monitoring, and for illustrating the physiologic basis and hemodynamic effects of therapeutic interventions. We will build on this foundation by using a cardiovascular simulator to illustrate the application of these principles in the care of patients with severe sepsis, cardiogenic shock, and acute mechanical circulatory support. DATA SOURCES: Publications relevant to the discussion of the time-varying elastance model, cardiogenic shock, and sepsis were retrieved from MEDLINE. Supporting evidence was also retrieved from MEDLINE when indicated. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: Data from relevant publications were reviewed and applied as indicated. CONCLUSIONS: The ventricular pressure-volume relationship and time-varying elastance model provide a foundation for understanding cardiovascular physiology and pathophysiology. We have built on this foundation by using a cardiovascular simulator to illustrate the application of these important principles and have demonstrated how complex pathophysiologic abnormalities alter clinical parameters used by the clinician at the bedside.

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.

The acute influence of vasopressin on hemodynamic status and tissue oxygenation following the Norwood procedure.

Objectives: Arginine vasopressin (AVP) is used to treat hypotension. Because AVP increases blood pressure by increasing systemic vascular resistance, it may have an adverse effect on tissue oxygenation following the Norwood procedure. Methods: Retrospective analysis of continuously captured hemodynamic data of neonates receiving AVP following the Norwood procedure. Results: We studied 64 neonates exposed to AVP within 7 days after the Norwood procedure. For the entire group, AVP significantly increased mean blood pressure (2.5 ± 6.3) and cerebral and renal oxygen extraction ratios (4.1% ± 9.6% and 2.0% ± 4.7%, respectively; P < .001 for all values). In the right ventricle to pulmonary artery shunt cohort, AVP significantly increased blood pressure, arterial oxygen saturation (1.4% ± 3.8%; P = .011), pulmonary to systemic perfusion ratio (0.2 ± 0.4; P = .017), and cerebral and renal oxygen extraction ratios (4.6% ± 8.7%; P = .010% and 4.7% ± 9.4%; P = .014, respectively). The Blalock-Taussig shunt cohort experienced a less significant vasopressor response and no change in arterial oxygen saturation, pulmonary to systemic perfusion ratio, or cerebral and renal oxygen extraction ratios. Conclusions: The right ventricle to pulmonary artery shunt cohort experienced a significant vasopressor response to AVP that was associated with a significant increase in pulmonary perfusion and decrease in cerebral and renal perfusion, whereas the Blalock-Taussig shunt cohort experienced a less significant vasopressor response and no change in pulmonary or systemic perfusion. The influence of AVP on tissue oxygenation following the Norwood procedure may have clinical implications that require further study.

Fluid bolus administration in children, who responds and how? A systematic review and meta-analysis.

BACKGROUND: Fluid boluses are frequently utilized in children. Despite their frequency of use, there is little objective data regarding the utility of fluid boluses, who they benefit the most, and what the effects are. AIMS: This study aimed to conduct pooled analyses to identify those who may be more likely to respond to fluid boluses as well as characterize clinical changes associated with fluid boluses. METHODS: A systematic review of the literature and meta-analysis was conducted to identify pediatric studies investigating the response to fluid boluses and clinical changes associated with fluid boluses. RESULTS: A total of 15 studies with 637 patients were included in the final analyses with a mean age of 650 days ± 821.01 (95% CI 586 to 714) and a mean weight of 10.5 kg ± 7.19 (95% CI 9.94 to 11.1). The mean bolus volume was 12.14 ml/kg ± 4.09 (95% CI 11.8 to 12.5) given over a mean of 19.55 min ± 10.16 (95% CI 18.8 to 20.3). The following baseline characteristics were associated with increased likelihood of response [represented in mean difference (95% CI)]: greater age [207.2 days (140.8 to 273.2)], lower cardiac index [-0.5 ml/min/m2 (-0.9 to -0.3)], and lower stroke volume [-5.1 ml/m2 (-7.9 to -2.3)]. The following clinical parameters significantly changed after a fluid bolus: decreased HR [-5.6 bpm (-9.8 to -1.3)], increased systolic blood pressure [7.7 mmHg (1.0 to 14.4)], increased mean arterial blood pressure [5.5 mmHg (3.1 to 7.8)], increased cardiac index [0.3 ml/min/m2 (0.1 to 0.6)], increased stroke volume [4.3 ml/m2 (3.5 to 5.2)], increased central venous pressure [2.2 mmHg (1.1 to 3.3)], and increased systemic vascular resistance [2.1 woods units/m2 (0.1 to 4.2)]. CONCLUSION: Fluid blouses increase arterial blood pressure or cardiac output by 10% in approximately 56% of pediatric patients. Fluid blouses lead to significant decrease in HR and significant increases in cardiac output, stroke volume, and systemic vascular resistance. Limited published data are available on the effects of fluid blouses on systemic oxygen delivery.

Impact of Noonan Syndrome on admissions for pediatric cardiac surgery.

BACKGROUND: Noonan Syndrome is the second most common genetic syndrome associated with congenital heart disease. Many patients with Noonan Syndrome will require a cardiac intervention. This study aimed to characterize the difference in cardiac surgery admissions in patients with and without Noonan Syndrome. METHODS: Data regarding hospital admissions was collected using the Kids' Inpatient Database from 1997 to 2012. A cross-sectional study was conducted comparing baseline characteristics, cardiac morphology, cardiac surgery, and other comorbidities between those with and without Noonan Syndrome. Regression analysis was conducted to determine factors related to Noonan Syndrome and risk factors for increased length of hospitalization, need for ECMO, and inpatient mortality using Noonan Syndrome as the independent variable. RESULTS: A total of 46,169 admissions with cardiac surgery under 18 years of age were included in the final analyses. Of these 778 (1.6%) had Noonan Syndrome. Pulmonary stenosis, coronary anomalies, and valvuloplasty without valve replacement were independently associated with Noonan Syndrome. Those with Noonan Syndrome were 90% more likely to have chylothorax. Pediatric cardiac surgery admissions tended to be 4.5 days longer and cost $54,296 more in total charges with Noonan Syndrome. Inpatient mortality is also increased by Noonan Syndrome. CONCLUSIONS: Noonan Syndrome is present in a relatively small proportion of pediatric cardiac surgery admissions. Noonan Syndrome is independently associated with increased length and cost of such admissions as well as inpatient mortality.

Impact of sodium bicarbonate therapy on hemodynamic parameters in infants: a meta-analysis.

OBJECTIVE: Sodium bicarbonate is a frequently used electrolyte for the acute treatment of metabolic acidosis in critically ill patients. We performed a systematic review and meta-analysis to determine the effect of sodium bicarbonate on hemodynamics, gas exchange and oximetry in critically children. METHODS: A systematic review of published manuscripts was conducted to identify studies of children who received sodium bicarbonate as part of the treatment for metabolic acidosis. A meta-analysis was then conducted to determine the impact of sodium bicarbonate on hemodynamics, gas exchange and oximetry. The following parameters were captured: base deficit, heart rate, mean arterial pressure, blood concentration of carbon dioxide, blood concentration of hydrogen ion, and pulse oximetry. RESULTS: A total of six studies with 341 patients were included in the analyses. All included studies were completed in critically ill infants with a mean age of 1.1 months. The mean dose of sodium bicarbonate was 1.7 meq/kg with a mean time of 67 min prior to repeat hemodynamics being collected after sodium bicarbonate administration. Base deficit significantly improved with a decrease of 2.80 (p = .001) and the partial pressure of carbon dioxide significantly decreased by a mean of -1.65 mmHg (p = .010). There was no change in heart rate, blood pressure, pH, partial pressure of oxygen, or saturation by pulse oximetry. CONCLUSION: Sodium bicarbonate has a statistically significant but not clinically significant impact on partial pressure of carbon dioxide and base deficit 60 min after sodium bicarbonate administration in critically ill infants. There is no difference noted in pH, partial pressure of oxygen, or saturation by pulse oximetry.

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.

Standardized Training for Physicians Practicing Pediatric Cardiac Critical Care.

OBJECTIVES: In the vast majority of Children's Hospitals, the critically ill patient can be found in one of three locations: the PICU, the neonatal ICU, and the cardiac ICU. Training, certification, and maintenance of certification for neonatology and critical care medicine are over seen by the Accreditation Council for Graduate Medical Education and American Board of Pediatrics. There is no standardization of training or oversight of certification and maintenance of certification for pediatric cardiac critical care. DATA SOURCES: The curricula from the twenty 4th year pediatric cardiac critical care training programs were collated, along with the learning objectives from the Pediatric Cardiac Intensive Care Society published "Curriculum for Pediatric Cardiac Critical Care Medicine." STUDY SELECTION: This initiative is endorsed by the Pediatric Cardiac Intensive Care Society as a first step toward Accreditation Council for Graduate Medical Education oversight of training and American Board of Pediatrics oversight of maintenance of certification. DATA EXTRACTION: A taskforce was established of cardiac intensivists, including the directors of all 4th year pediatric cardiac critical care training programs. DATA SYNTHESIS: Using modified Delphi methodology, learning objectives, rotational requirements, and institutional requirements for providing training were developed. CONCLUSIONS: In the current era of increasing specialized care in pediatric cardiac critical care, standardized training for pediatric cardiac critical care is paramount to optimizing outcomes.

Alpha-blockade during congenital heart surgery admissions: analysis from national database.

INTRODUCTION: The effects of alpha-blockade on haemodynamics during and following congenital heart surgery are well documented, but data on patient outcomes, mortality, and hospital charges are limited. The purpose of this study was to characterise the use of alpha-blockade during congenital heart surgery admissions and to determine its association with common clinical outcomes. MATERIALS AND METHODS: A cross-sectional study was conducted using the Pediatric Health Information System database. De-identified data for patients under 18 years of age with a cardiac diagnosis who underwent congenital heart surgery were obtained from 2004 to 2015. Patients were subdivided on the basis of receiving alpha-blockade with either phenoxybenzamine or phentolamine during admission or not. Continuous and categorical variables were analysed using Mann−Whitney U-tests and Fisher exact tests, respectively. Characteristics between subgroups were compared using univariate analysis. Regression analyses were conducted to determine the impact of alpha-blockade on ICU length of stay, hospital length of stay, billed charges, and mortality. RESULTS: Of the 81,313 admissions, 4309 (5.3%) utilised alpha-blockade. Phentolamine was utilised in 4290 admissions. In univariate analysis, ICU length of stay, total length of stay, inpatient mortality, and billed charges were all significantly higher in the alpha-blockade admissions. However, regression analyses demonstrated that other factors were behind these increased. Alpha-blockade was significantly, independently associated with a 1.5 days reduction in ICU length of stay (p < 0.01) and a 3.5 days reduction in total length of stay (p < 0.01). Alpha-blockade was significantly, independently associated with a reduction in mortality (odds ratio 0.8, 95% confidence interval 0.7−0.9). Alpha-blockade was not independently associated with any significant change in billed charges. CONCLUSIONS: Alpha-blockade is used in a subset of paediatric cardiac surgeries and is independently associated with significant reductions in ICU length of stay, hospital length of stay, and mortality without significantly altering billed charges.

Correlation of Near-Infrared Spectroscopy Oximetry and Corresponding Venous Oxygen Saturations in Children with Congenital Heart Disease.

Invasive and non-invasive monitoring allow for early detection of hemodynamic compromise, facilitating timely intervention and avoidance of further decline. While venous oximetry is useful for assessing the adequacy of systemic oxygen delivery (DO2), it is most often intermittent, invasive, and costly. Near-infrared spectroscopy (NIRS) oximetry allows for the non-invasive estimation of the adequacy of DO2. We assessed the correlation between cerebral NIRS oximetry and superior vena cava (SVC) and jugular venous (JV) oxygen saturations and between renal NIRS oximetry and inferior vena cava (IVC) oxygen saturations. Systematic review of the literature was conducted to identify studies with data regarding near-infrared spectroscopy and venous saturation. The PubMed, EMBASE, Medline, and Cochrane databases were queried using the following terms in isolation and various combinations: "congenital heart disease," "near infrared spectroscopy," "venous saturation," and "pediatric." Pediatric studies in which simultaneous NIRS oximetry and corresponding venous oxygen saturations were simultaneously collected after cardiac surgery or catheterization were identified. Data were pooled from these studies to analyze the correlation between NIRS oximetry and the corresponding venous oxygen saturations. A total of 16 studies with 613 patients were included in the final analyses. Data were present to compare cerebral and renal NIRS oximetry with corresponding venous oxygen saturation. Cerebral NIRS and SVC and JV oxygen saturations and renal NIRS and IVC oxygen saturations demonstrated strong degrees of correlation (r-value 0.70 for each). However, cerebral NIRS and IVC oxygen saturation had a week degree of correlation (r-value of 0.38). Pooled analyses demonstrate that cerebral NIRS oximetry correlates strongly with SVC or JV oxygen saturation while renal NIRS oximetry correlates strongly with IVC oxygen saturations. A weak correlation was noted between cerebral NIRS oximetry and IVC oxygen saturations.

Acute Effects of Vasopressin Arginine Infusion in Children with Congenital Heart Disease: Higher Blood Pressure Does Not Equal Improved Systemic Oxygen Delivery.

The use of vasopressin has been increased in recent years in children after congenital heart surgery. However, there is limited information regarding its effects on cardiac output, systemic oxygen delivery, and myocardial energetics. The purpose of this study is to characterize the effects of vasopressin infusions on hemodynamics and systemic oxygen delivery in children with congenital heart disease. A retrospective, single-center study of patients with congenital heart disease who received vasopressin infusions in a pediatric cardiac intensive care unit between January 2019 and May 2020. The measured values collected for study were systolic and diastolic blood pressure, heart rate, arterial oxygen saturation as determined by pulse oximetry, arterial pH, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, serum lactate, serum sodium, and renal and cerebral oximetry based on near-infrared spectroscopy. The calculated values for this study were the difference between arterial and NIRS oximetry, the reno-cerebral near-infrared spectroscopy gradient and the vasoinotrope score. A Wilcoxon signed-rank test was utilized to compare values of paired continuous variables before and after initiation of the vasopressin infusion. Correlations were assessed using Spearman correlation analyses and stepwise regressions were completed. A total of 26 vasopressin infusions among 20 unique patients were included in the final analyses. Of these 26 vasopressin infusions, 18 were in patients with biventricular circulation and 8 were in patients with functionally univentricular circulation. The median vasopressin infusion dose at initiation was 0.4 (0.1-1) milliunits/kg/min. For the entire cohort 2 h after the initiation of vasopressin, systolic blood pressure increased to 8.4 mmHg, p < 0.01, but no significant correlation was found to markers of systemic oxygen delivery. Similar results were obtained when only those with biventricular circulation were considered. Those with functionally univentricular circulation were not found to have any statistically significant rise in blood pressure. Vasopressin infusions appear to statistically significantly increase systolic blood pressure in children with congenital heart disease who have a biventricular but not functionally univentricular circulation. Even when an increase in systolic blood pressure is present, systemic oxygen delivery did not improve.

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.