October

Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients

[et_pb_section fb_built="1" admin_label="section" _builder_version="3.22"][et_pb_row admin_label="row" _builder_version="3.25" background_size="initial" background_position="top_left" background_repeat="repeat"][et_pb_column type="4_4" _builder_version="3.25" custom_padding="|||" custom_padding__hover="|||"][et_pb_text admin_label="Text" _builder_version="3.27.4" background_size="initial" background_position="top_left" background_repeat="repeat"]Section Editors  Viviane Nasr - Boston         Rania Abbasi - Indianapolis       Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients Sheldon Stohl 1 2, Margaret J Klein 3, Patrick A Ross 3 4, Sabine vonBusse 3 5, JonDavid Menteer 4 6 Pediatr Cardiol. 2020 Jun;41(5):962-971.  doi: 10.1007/s00246-020-02344-9. Epub 2020 Jun 18. PMID: 32556487; DOI: 10.1007/s00246-020-02344-9   Take Home Points:   Serial cardiac catheterizations in pediatric cardiac transplant recipients are performed as routine surveillance. The chosen anesthetic and ventilatory strategies may alter neutral hemodynamic conditions and thereby confound interpretation of catheterization results. This retrospective, single center cohort study reviewed the effects of different anesthetic and ventilatory strategies on hemodynamic variables measured during cardiac catheterization. Observations: Positive pressure ventilation, irrespective of anesthetic technique, lowers cardiac output but does not affect filling pressures or pulmonary vascular resistance. In contrast to moderate sedation, general anesthesia increases left-sided filling pressures and lowers SVR. These differences are quantitatively small and of limited clinical significance, which should be taken into consideration when comparing and interpreting hemodynamic catheterization results.     Commentary from Dr. Anne Elisa Cossu, MD, pediatric cardiac anesthesiologist at Children’s Hospital of the King’s Daughters in Norfolk, VA: Pediatric cardiac transplant recipients undergo consecutive invasive hemodynamic catheterizations as part of their routine clinical surveillance to guide treatment, inform prognostic discussion and screen for cellular and humoral rejection. Catheterization in pediatric patients is typically accomplished under moderate sedation or general anesthesia. It is known that hypnotic and anesthetic agents as well as ventilatory conditions can alter hemodynamic measures. However, the degree to which these conditions influence variables measured during cardiac catheterization is unknown in pediatric patients. The aim of this study was to assess the effects of anesthetic agents and ventilation on hemodynamic measures of the pediatric orthotopic heart.   The study is a retrospective, single center cohort study of non-critically ill pediatric heart transplant patients. Catheterization records from all pediatric heart transplant recipients were reviewed from January 2005 to December 2017. All hemodynamic catheterizations performed in the study period were eligible for inclusion. Catheterizations were excluded on critically ill patients, patients on vasoactive support, patients with New York Heart Association Class II functional capacity or worse, patients with biopsy results revealing significant cellular or humoral rejection or patients with coronary angiography revealing greater than mild cardiac allograft vasculopathy. Other catheterizations were excluded for severe upper airway obstruction or poor intraprocedural ventilation and those in which hemodynamic data could not be found accurately in the medical record. Catheterizations were divided into two groups, spontaneous ventilation and positive pressure ventilation. The spontaneous ventilation group was further divided into moderate sedation versus general anesthesia to assess for the confounding effects of anesthetic depth. The positive pressure ventilation group was further divided into controlled ventilation versus pressure support ventilation. Primary outcome measures included cardiac index (CI) as measured by thermodilution; right and left heart filling pressures as indicated by right ventricular end-diastolic pressure (RVEDP) and pulmonary capillary wedge pressure (PCWP); and pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR).   720 catheterizations from 101 recipients met the inclusion criteria and were included in statistical analysis. Medications used for general anesthesia included propofol, sevoflurane, isoflurane, desflurane or combinations thereof. Moderate sedation employed midazolam, fentanyl, and ketamine. CI was higher with spontaneous versus positive pressure ventilation (3.14 vs 2.71 L/min/m2, p< 0.0001), independent of depth of anesthesia (sedation versus general anesthesia). When comparing RVEDP (7.0 vs 7.7 mm Hg, p= 0.11) and PVR (2.1 vs 2.3 Woods units, p=0.29) between spontaneous and positive pressure ventilation, the differences did not reach statistical significance. Similarly, no significant differences were detected between spontaneous versus positive pressure ventilation in fully anesthetized patients. PCWP was lower (9.9 vs 11.0 mm Hg, p=0.03) and SVR was higher (24.0 vs 20.5 Woods units, p < 0.0001) with spontaneous ventilation versus positive pressure ventilation. Further analysis of subgroups revealed that moderate sedation was associated with lower PCWP and higher SVR than general anesthesia.   This study sheds light on the potential hemodynamic alterations expected in the presence of different anesthetic and ventilatory conditions. CI was 15% higher with spontaneous versus positive pressure ventilation, supportive of the observation that negative pleural pressure increases cardiac output. Conversely, filling pressures and vascular resistance were less affected by ventilation method versus anesthetic technique. Left-sided filling pressures (PCWP) were approximately 15% lower and SVR 20% higher with moderate sedation versus general anesthesia, irrespective of ventilation mode. These observed differences were small and should inform practitioners that variations in ventilation and anesthetic strategy should not alter diagnostic results radically between one catheterization and another.   The study was observational versus a controlled physiologic experiment and therefore, attempts to explain hemodynamic differences between anesthetized and sedated patients is only speculative. Lower filling pressures in sedated patients could be explained by mild upper airway obstruction and increased negative intrathoracic pressure. In this study, moderate sedation was given by a nurse and perhaps the presence of a trained anesthesiologist may alleviate airway obstruction that may attend moderate sedation. SVR was lower in patients who received general anesthesia, which supports published literature on the vasodilatory effects of general anesthetics. Lack of lower PVR in the patients who received general anesthesia was an unexpected result, as the inhalational anesthetics are known to blunt hypoxic pulmonary vasoconstriction.   Due to the retrospective nature of this study, there may be sources of bias in the study. The authors felt that selection bias and systematic bias were unlikely. However, the anesthetists’ choice of ventilation strategy could have been influenced pre-procedurally by patients deemed to have better or worse hemodynamics. Younger patients were more often managed with general anesthesia and positive pressure ventilation. Another limitation of the study is that there was a gross estimate of anesthetic depth as general anesthesia. Patients allowed to breath spontaneously under general anesthesia could have received less anesthetic agent than those under positive pressure ventilation. Additionally, patients paralyzed with neuromuscular blockers may also require less anesthetic than their nonparalyzed counterparts. As evident from the results, depth of anesthesia surely influences hemodynamic measures. Additionally, the study was not powered to compare different anesthetic regimens in the moderate sedation and general anesthesia groups. The study does not account for sub-clinical changes in patients over time in functional capacity, ventricular function or for medication changes, however the exclusion criteria would have blunted these confounders. As a final point, the study did not record tidal volumes; hyper or hypoinflation could have negatively impacted PVR and right ventricular function.   In conclusion, positive pressure ventilation, irrespective of anesthetic technique, lowers cardiac output but does not affect filling pressures or pulmonary vascular resistance in pediatric orthotopic heart transplant patients. In contrast to moderate sedation, general anesthesia increases left-sided filling pressures and lowers SVR. These differences are quantitatively small and of limited clinical significance, which should be taken into consideration when comparing and interpreting hemodynamic catheterization results.          [/et_pb_text][/et_pb_column][/et_pb_row][/et_pb_section]

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Risk Factors for Peri-Intubation Cardiac Arrest in Pediatric Cardiac Intensive Care Patients: A Multicenter Study

[et_pb_section fb_built="1" admin_label="section" _builder_version="3.22" min_height="4719px" custom_padding="0px|||||"][et_pb_row admin_label="row" _builder_version="3.25" background_size="initial" background_position="top_left" background_repeat="repeat" min_height="4439px"][et_pb_column type="4_4" _builder_version="3.25" custom_padding="|||" custom_padding__hover="|||"][et_pb_text admin_label="Text" _builder_version="3.27.4" background_size="initial" background_position="top_left" background_repeat="repeat" min_height="4480px"]Section Editors  Viviane Nasr - Boston         Rania Abbasi - Indianapolis       Risk Factors for Peri-Intubation Cardiac Arrest in Pediatric Cardiac Intensive Care Patients: A Multicenter Study.   Esangbedo ID, Byrnes J, Brandewie K, Ebraheem M, Yu P, Zhang S, Raymond T.Pediatr Crit Care Med. 2020 Dec;21(12):e1126-e1133. doi: 10.1097/PCC.0000000000002472.PMID: 32740187   Take-Home Points:   The frequency of peri-intubation cardiac arrest (PICA) in the cardiac intensive care unit (ICU) is high among critically ill children with congenital and acquired heart disease. In the cohort of children with cardiac disease, moderate to severe systolic dysfunction of the systemic ventricle, pre-intubation hypotension, lactic acidosis > 10 mmol/L, and pH< 7.0 are found to be risk factors associated with PICA.       Commentary from Venu Amula MD, Pediatric Cardiac Intensivist at Primary Children’s Hospital/University of Utah SLC, Utah:  The transition from spontaneous to positive pressure ventilation during endotracheal intubation is challenging for critically ill infants and children. The acute change in intrathoracic pressure and ventricular loading conditions, coupled with the pharmacological effects of medications used during intubation, can result in adverse hemodynamic consequences. Patients with low hemodynamic reserve owing to cardiac disease are more vulnerable, given that they sometimes operate at the extremes of physiologic compensation.   Peri-intubation cardiac arrest (PICA), defined as cardiac arrest requiring chest compressions for > 1 min and occurring during and within 30 minutes of the procedure, has adverse outcomes in the adult population with high immediate and 28-day mortality. Pre-intubation hypoxia and hypotension are identified as risk factors associated with PICA in adults. In children, studies using National Emergency Airway Registry for Children (NEAR4Kids) show a PICA rate of 1.7% among all pediatric intensive care patients with higher rates in those with a cardiac diagnosis than without (2.8% vs. 1.8%). Studies evaluating intubations in dedicated cardiac ICUs are lacking.   The authors of this multicenter retrospective cohort study aimed to evaluate the characteristics and frequency of PICA in critically ill children with cardiac disease cared for in three specialized cardiac ICUs. They also sought to identify risk factors associated with PICA. The primary outcome of interest is the frequency of PICA. Pediatric patients (0-18 yrs.) with congenital and acquired heart disease undergoing endotracheal intubation between January 2015 and December 2017 were retrospectively reviewed in this study. Patient, provider, and procedural characteristics of intubation events that resulted in cardiac arrest were compared with those that did not (comparison groups) using the two-sample t-test and chi-square test. Patients were excluded for the following reasons: intubation outside the cardiac ICU, prior cardiac arrest, intubation as part of tube exchange, current ECMO requirement, elective intubation performed by an anesthesiologist, and incomplete data.   A total of 186 intubation events were identified that occurred in 151 pts over the study period. The median age of the patients was 3.1 months, and the median weight was 4.3 kg. Seventy-one of the 186 events occurred in those with associated non-cardiac morbidity, and 28 occurred in those with a genetic syndrome. The majority of the intubations were presurgical, while 40% occurred within one month of cardiac surgery. Immediate indications for intubation were (in the order of frequency): hypoxemia, work of breathing, hypercarbia, shock, and metabolic acidosis. The indications did not differ between the groups. Etiologies of arrest as recorded were: prolonged hypoxia, worsened acidosis, medications, and misplaced endotracheal tube.   The primary outcome of PICA occurred in 13/186 cases with a rate of 7%. This rate was 21% among the subgroup with moderate to severe systolic dysfunction of the systemic ventricle. The most common rhythms at arrest were bradycardia and pulseless electrical activity. The median duration of cardiopulmonary resuscitation was 10 min (IQR 4.5- 21 min). Among the 13 patients who had a cardiac arrest episode, 7 had a return of circulation without extracorporeal membrane oxygenation (ECMO), 3 had a return of circulation with ECMO, and 3 died.   Upon comparing arrest and the non-arrest events, pre-intubation hypotension (60 vs 18.4%, p=0.007), moderate to severe left ventricular dysfunction (23 vs 8.5%, p=0.048), pre-intubation lactate > 10 mmol/L (25 vs 6% ,p=0.018) and pH < 7.0 (23 vs 4.1 % , p=0.036) were significantly higher in the PICA group. Procedural and provider characteristics, including the number of attempts, video laryngoscopy, clinician performing the procedure, were not significantly different between the two groups. The type of medications used also did not differ.   What does this mean for us?    Few studies from large registries show that cardiac arrest associated with intubation is more likely to occur in critically ill children with cardiac disease. These studies provide limited details of patient, provider, and procedural characteristics. The authors in the current study attempted to characterize PICA in children with acquired and congenital heart disease cared for in dedicated cardiac ICUs. They found a higher frequency of PICA in the study population when compared to published literature, and they identified patient characteristics significantly associated with the cardiac arrest.   While the study emphasizes the possibility of adverse events associated with intubation in children with cardiac disease, the conclusions need to be read cautiously. Though multicentric, the study is conducted only in three cardiac ICUs and thus lacks generalizability. As acknowledged by the authors, the other major limitation of the study is the small sample size. The retrospective and observational nature of this study lend to selection bias in both directions, and the usual strategies to adjust for confounding effects of variables is limited by the rare occurrence of the primary outcome event (cardiac arrest) in relation to the predictor variables, i.e., few events per predictor variable. It is difficult to reliably assess the risk of cardiac arrest with the study variables though statistical association exists in unadjusted models.   Regardless of its limitations, the study brings two points to light concerning intubation in children with cardiac disease. Both focus on anticipatory management   1)  Early recognition of hemodynamic and respiratory perturbations (before the anaerobic threshold for oxygen delivery sets in) is critical in children with heart disease, particularly those with significant systolic dysfunction. A timely decision to intubate while some respiratory and hemodynamic reserve remains may mitigate adverse events.   2)  If a child in the cardiac ICU needs intubation and the multiple risk factors identified in this study are already established, thoughtful consideration of pharmacologic and personnel management is vital. The strategy may include calling for anesthesia backup to establish airway quickly and having the team prepared for advanced cardiopulmonary resuscitation if need arises.   The authors should be congratulated for bringing these focus points to the forefront, and future studies with different centers may be worthwhile.      [/et_pb_text][/et_pb_column][/et_pb_row][/et_pb_section]

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Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass

[et_pb_section fb_built="1" admin_label="section" _builder_version="3.22" width="100%" min_height="4496px"][et_pb_row admin_label="row" _builder_version="3.25" background_size="initial" background_position="top_left" background_repeat="repeat" min_height="4335px"][et_pb_column type="4_4" _builder_version="3.25" custom_padding="|||" custom_padding__hover="|||"][et_pb_text admin_label="Text" _builder_version="3.27.4" background_size="initial" background_position="top_left" background_repeat="repeat" custom_margin="-106px|||||"]Section Editors  Viviane Nasr - Boston         Rania Abbasi - Indianapolis       Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass Chawki Elzein 1, Cynthia Urbas 2, Bonnie Hughes 3, Yi Li 4, Cheryl Lefaiver 5, Michel Ilbawi 1, Luca Vricella 1 World J Pediatr Congenit Heart Surg. 2020 Jul;11(4):417-423. doi: 10.1177/2150135120911034. PMID: 32645771; DOI: 10.1177/2150135120911034   Take Home Points: Administration of nitric oxide (NO) during cardiopulmonary bypass (CPB) resulted in lower troponin levels after weaning from CPB than those who did not receive NO, with lower level prior to modified ultrafiltration (MUF) and significantly lower levels after conclusion of MUF Compared to the control group, there was no significant difference in inotropic scores or ventricular function during the 24-hour postoperative study period in those who received NO during CPB Systemic administration of NO during CPB for the Norwood procedure has myocardial protective effects (lower Troponin levels) but no observed effect on postoperative recovery Commentary from Dr. Rajeev Wadia, Assistant Professor of Pediatric Cardiac Anesthesiology at Johns Hopkins University: Cardiopulmonary bypass (CPB) creates morbidity in all patient populations. The absence of pulsatile flow, episodes of circulatory arrest or low-flow periods, complexity of congenital heart surgery with long bypass times, and the immature organs of a neonate all result in systemic inflammation in the neonate. Ischemia/reperfusion injury is a known producer of pro-inflammatory mediators that cause systemic organ dysfunction. Nitric oxide (NO) can provide protection to ischemia/reperfusion injuries. In adult patients undergoing CPB surgery, NO has been shown to blunt the release of markers of cardiac injury and decrease ventricular dysfunction during and immediately after CPB (1, 2). Furthermore, it has been shown that infants undergoing repair of tetralogy of Fallot who received NO during CPB had evidence of better myocardial protection, improved fluid balance, and improved postoperative intensive care unit course (3). The authors of this manuscript hypothesized that systemic delivery of NO into the oxygenator of the CPB circuit during the Norwood procedure would ameliorate ischemia/reperfusion injury and improve postoperative recovery. They performed a prospective, randomized, blinded control study of newborns undergoing a Norwood operation with a Sano shunt at a single institution in the United States over an approximate 4-year time period. The study was sponsored by Mallinckrodt Pharmaceuticals (Hampton, NJ). A total of 24 neonates with hypoplastic left heart syndrome or variants participated in the study, with one-half randomly assigned to receive 40 ppm NO through the oxygenator (study group, n=12) and the other one-half to receive a placebo gas (control group, n=12). All patients were required to be > 37 weeks gestation and have a birth weight of > 2.5 kg. Patients were excluded if they had perioperative sepsis, renal dysfunction (creatinine level >1 mg/dL), intracranial hemorrhage, presence of chromosomal abnormalities and/or genetic syndromes, and prior intervention (catheter or surgical).    The intraoperative care these neonates received is worth noting. All neonates received a total of 20 mg/kg of methylprednisolone prior to surgical incision, in equally divided doses 6-8 hours apart. All patients received continuous cerebral perfusion at 50 ml/kg/min through cannulation of the base of the innominate artery and continuous perfusion of the lower part of the body at 50 ml/kg/min through cannulation of the descending aorta after the distal aspect of the arch patch was sutured. The authors report that in their experience when using this lower body cannulation technique, interruption of blood flow to the lower body is limited to approximately 20 minutes. No patient, therefore, had total circulatory arrest. The heads and groins were routinely covered with ice bags until rewarming was started. All patients were cooled to 28⁰C. Cooling and rewarming were done using pH-stat strategy. Finally, once the patients were weaned off CPB, NO (or placebo gas) administration within the CPB machine was discontinued. All patients, both control and study participants, were then administered inhaled NO through the endotracheal tube. Subsequent inhaled NO management was similar among all patients per routine institutional practice. Only the perfusionist was aware of the randomization process. No other practitioners in either the operative or postoperative location knew who received NO or placebo gas through the CPB circuit. All patients had skin closure in the operating room with delayed sternal closure a few days after adequate diuresis. There was no difference in demographic characteristics or surgical times between the groups. All operations were performed by the same two surgeons using the same technique. Of note, the total mean time of flow interruption of the lower body was not different between either group (study group: 19.2 ± 6.74 min vs control group: 18.0 ± 3.62 min). No patient died in the study.         Serum samples measuring multiple inflammatory markers were taken at 5 different time points (T0: after induction of general anesthesia but before surgery, T1: after weaning off CPB but before MUF, T2: after MUF, T3: 12 hours after CPB discontinuation, T4: 24 hours after CPB discontinuation). Results for both groups are shown in Table 2. The study group had lower troponin levels at the end of CPB compared to the control group (0.62 ± 0.58 vs 0.87 ± 0.58, p=0.31) and the difference became significant at the end of modified ultrafiltration (MUF) (0.36 ± 0.32 vs 0.97 ± 0.48, p=0.009). Clinical outcome data collected for both groups showed no difference in inotropic scores or ventricular function, despite the lower troponin levels noted in the study group. Furthermore, there was no difference in the duration of mechanical ventilation, pediatric surgical heart unit length of stay, and hospital length of stay.               The authors admit their study has several important limitations. They had a small sample size from a single center, requiring nearly 4 years to recruit enough patients. Despite this, the study still did not meet its primary end point based on the power calculation required to compare the difference in fluid balance, as measured by the total amount of fluid administered in the first 24 and 48 hours. Also, the surgical technique used for selective cerebral and lower body perfusion may have limited the ischemia time, thus decreasing the ischemia/reperfusion injury in the control group. Finally, the routine use of inhaled NO in the postoperative period may have added some protection to both groups and decreased the power of the study. Even so, this pilot study does show that perhaps NO administration during CPB in high-risk, single-ventricle population could confer myocardial protective effect. However, in order to show any long-term clinical benefit, a larger number of patients would be necessary. References: Table 2. Comparison Between I/R Injury Markers at Different Time Points Between Both Groups. Johansen JV, Sato H, Zhao ZQ. The role of nitric oxide and NO-donor agents in myocardial protection from surgical ischemic-reperfusion injury. Int J Cardiol. 1995;50(3): 273-281 Lefer AM. Attenuation of myocardial ischemia-reperfusion injury with nitric oxide replacement therapy. Ann Thorac Surg. 1995;60(3):847-851 Checchia PA, Bronicki RA, Muenzer JT, DixonD. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children – a randomized trial. J Thorac Cardiovasc Surg. 2013;146(3):530-536  [/et_pb_text][/et_pb_column][/et_pb_row][/et_pb_section]

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Age over 35 years is associated with increased mortality after pulmonary valve replacement in repaired tetralogy of Fallot: results from the UK National Congenital Heart Disease Audit database.

Age over 35 years is associated with increased mortality after pulmonary valve replacement in repaired tetralogy of Fallot: results from the UK National Congenital Heart Disease Audit database.   Dorobantu DM, Sharabiani MTA, Taliotis D, Parry AJ, Tulloh RMR,...

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Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients

Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients Sheldon Stohl 1 2, Margaret J Klein 3, Patrick A Ross 3 4, Sabine vonBusse 3 5, JonDavid Menteer 4 6 Pediatr Cardiol. 2020 Jun;41(5):962-971....

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