Near-Infrared Spectroscopy in Neonates Before Palliation of Hypoplastic Left Heart Syndrome

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1 Near-Infrared Spectroscopy in Neonates Before Palliation of Hypoplastic Left Heart Syndrome Beth Ann Johnson, MD, George M. Hoffman, MD, James S. Tweddell, MD, Joseph R. Cava, MD, PhD, Mir Basir, MD, Michael E. Mitchell, MD, Matthew C. Scanlon, MD, Kathleen A. Mussatto, BSN, PhDc, and Nancy S. Ghanayem, MD Herma Heart Center, Children s Hospital of Wisconsin, Divisions of Cardiology, Critical Care, Neonatology, and Quantitative Health Sciences, Department of Pediatrics, Department of Anesthesia, and Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin Background. Neonates with hypoplastic left heart syndrome have circulatory vulnerability that results in shock and high risk of mortality without intervention. High arterial saturation (SaO 2 ) is often used as a proxy for inadequate systemic oxygen delivery and triggers the use of invasive therapies to restore circulatory balance. We hypothesized that preoperative use of near-infrared spectroscopy (NIRS) would reduce the need for invasive therapies, including controlled ventilation and inspired gas manipulation. Methods. A Human Research Review Board approved retrospective review of patients who had stage 1 palliation from Januar 2000 to January 2006 was conducted. Preoperative patient characteristics, cardiorespiratory support, and monitored data were collected for all patients. Cerebral and somatic tissue oxyhemoglobin saturations were recorded for patients with preoperative NIRS monitoring. Results. The studied cohort included 92 patients, 47 without and 45 with preoperative NIRS. Patient characteristics were similar between groups. Differences were observed in preoperative respiratory support. Controlled ventilation was less common in the NIRS group (51% versus 79%, p 0.005) as was the use of inspired nitrogen (16% versus 70%, p 0.001). The NIRS patients had higher mean SaO 2 (92% versus 88%, p 0.001). Age at surgery was similar between groups ( versus days, p 0.3). Early survival was 96% in each group. Conclusions. Near-infrared spectroscopy monitoring of patients with hypoplastic left heart syndrome awaiting palliation provides noninvasive assessment of oxygen delivery and simplified management, with reduced use of controlled ventilation and inspired gas. Higher SaO 2 in the NIRS group was not associated with impaired systemic oxygen delivery, and did not lead to earlier palliation or postoperative mortality. (Ann Thorac Surg 2009;87:571 9) 2009 by The Society of Thoracic Surgeons The preoperative patient with hypoplastic left heart syndrome (HLHS) faces similar physiologic challenges as are observed after the Norwood operation (stage 1 palliation): critical impairment of systemic oxygen delivery from obligate arterial desaturation, inefficiency of parallel circulation, aortopulmonary runoff, and morphologic and functional limitations on ventricular function. As a result, preoperative management commonly relies on arterial saturation as a proxy measure of optimum systemic oxygen delivery before stage 1 palliation. We have previously shown that arterial saturation is a poor predictor of oxygen delivery and that measurement of venous saturation predicts the development of shock and reduces postoperative morbidity and mortality [1 3]. Two-site near-infrared spectroscopy (NIRS) can Accepted for publication Oct 14, Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 30, Address correspondence to Dr Ghanayem, Children s Hospital of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI 53226; nancyg@mcw.edu. provide a noninvasive continuous estimate of venous saturation and can detect changes in organ perfusion in the perioperative period [4, 5]. This study describes the clinical utility of two-site NIRS in the preoperative patient with HLHS. Patients and Methods Patients Human Research Review Board approval was obtained and parental consent was waived for a retrospective chart review of patients admitted with HLHS from January 2000 through January The focus of this review was 92 patients with HLHS as defined by the International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease [6]. Patients were excluded if the diminutive left ventricle Drs Hoffman and Ghanayem disclose that they have a financial relationship with Somanetics by The Society of Thoracic Surgeons /09/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 572 JOHNSON ET AL Ann Thorac Surg PREOPERATIVE NIRS IN HLHS 2009;87:571 9 Table 1. Patient Characteristics and Operative Data Control n 47 NIRS n 45 p Value Male 28 (60) 30 (67) 0.5 Gestational age at delivery, weeks Number preterm 5 5 ( 37 weeks) Birth weight, kg Weight 2.5 kg, n (%) 3 2 Prenatal diagnosis, n (%) 22 (47) 29 (64) 0.09 Inborn, n (%) 22 (47) 25 (56) 0.4 Intubated at admission, 22 (47) 19 (42) 0.7 n (%) Initial ph Age at surgery (days) Age 7 days, n (%) 39 (83) 38 (84) Age 7 days, n (%) 8 (17) 7 (16) Modified Blalock-Taussig shunt, n Right ventricle to pulmonary artery conduit, n Early (30-day) survival 45 (95.7%) 43 (95.6) 1 NIRS near-infrared spectroscopy. was of borderline size or if a two-ventricle repair was initially attempted. Patients with additional noncardiac disease, prematurity, or low birthweight were not excluded. This cohort was divided into two groups for primary analysis: the control group, which included 47 patients who were managed without preoperative NIRS; and a NIRS group, which included 45 patients who had NIRS monitoring as an adjunct to preoperative management. The transition to NIRS monitoring between the control and the NIRS groups was dependent on monitor availability and follows a chronologic pattern: January 2000 to May 2002, NIRS was not used at Children s Hospital of Wisconsin for preoperative monitoring (n 35); May 2002 to November 2003, NIRS was used sporadically and was dependent upon monitor availability (n 20, 8 patients with NIRS monitoring); and November 2003 to January 2006, NIRS was adopted as the standard of care for the preoperative management of all patients with HLHS (n 37). Monitoring and Data Collection Standardized cardiorespiratory monitoring for preoperative care of all patients with HLHS included pulse oximetry, continuous electrocardiogram, blood pressure, capnography when endotracheally intubated, intermittent blood gas analysis, and end-organ function laboratory values. With the deployment of NIRS monitors (Invos 5100; Somanetics, Troy, MI), probes were placed on the forehead and on the T10-L2 flank region as an attempt to capture circulations under autoregulatory (cerebral) and autonomic (somatic, renal, or splanchnic) control [5]. A detailed chart review was performed for patient characteristics, hourly details of respiratory support, administered medications, and laboratory values including arterial blood gases, hemoglobin and hematocrit, electrolytes, blood urea nitrogen, and creatinine. Hourly hemodynamic data recorded for the entire cohort included heart rate, systolic, diastolic, and mean arterial blood pressure, arterial saturation as detected by pulse oximetry (SaO 2 ), end-tidal carbon dioxide, and respiratory rate. In patients with NIRS monitoring, hourly cerebral and somatic oxyhemoglobin saturation (rso 2 ) data were also recorded. Statistical Analysis Data are reported as mean SD for continuous variables and count with percent for categorical variables. Median values with ranges are included where appropriate. For continuous data, nonparametric tests were performed when indicated by skewness of the data. To assess differences between groups, a Kruskal-Wallis or parametric analysis of variance was performed, and if this was significant, with Mann-Whitney posttests when appropriate. Fisher s exact test was used for comparing two groups, owing to the small expected cell sizes for some groups. Comparison of mean values for hemodynamic variables and support levels between groups was as- Table 2. Preoperative Data and Support Control n 47 NIRS n 45 p Value Intubated ever, n (%) 39 (83) 27 (60) Intubated day of surgery, n (%) 37 (79) 23 (51) Intubation duration for group, hours Median (range) 69 (0 154) 36 (0 208) Mean SD Intubation duration for intubated patients Mean (range) 73 (16 154) 88 (4 208) Mean, hours FiO Inspired CO 2, n (%) 0 2 (4) Inspired nitrogen, n (%) 33 (70) 7 (16) Duration nitrogen use, hours Arterial saturation (SpO 2 ) Cerebral rso Somatic rso Mean arterial blood pressure Inotropic score at first hour Inotropic score at day of surgery Caffeine, n (%) 0 17 (38) Milrinone, n (%) 0 4 (9) Preoperative transfusion, n (%) 14 (30) 21 (47) Initial creatinine Creatinine day of surgery FiO 2 fraction of inspired oxygen; rso 2 oxyhemoglobin saturation. NIRS near-infrared spectroscopy;

3 Ann Thorac Surg JOHNSON ET AL 2009;87:571 9 PREOPERATIVE NIRS IN HLHS 573 Table 3. Indications for Intubation Control (n) NIRS (n) Restrictive septum 4 2 High SaO Shock 9 8 Apnea 3 4 Respiratory distress 4 2 NIRS near-infrared spectroscopy. sessed by generalize least squares time-series regression. The cutoff for significance was p less than 0.05 after multiple comparison correction using Tukey s honestly significant difference, or Bonferroni s method, when applicable. Actuarial survival analysis was performed using Kaplan-Meier methods. Data were analyzed using STATA statistical software 10 (Stata, College Station, TX) and SPSS software 15.0 (SPSS, Chicago, IL). Results This initial review identified 116 consecutive patients with HLHS who underwent stage 1 surgical palliation from January 2000 to January Twenty-four patients were excluded from this analysis: 3 patients with a borderline left ventricle who had initial attempts at Fig 2. Standard hemodynamic measurements in patients managed with (dashed line) and without (solid line) near-infrared spectroscopy (NIRS). There were no significant differences except for a reduction in creatinine in NIRS-monitored patients. (BP blood pressure; ns not significant.) two-ventricle repair, and 21 patients with a dominant left or indeterminant ventricle. Patient Characteristics The studied cohort included 92 patients: 47 patients who did not have preoperative NIRS monitoring (control group), and 45 patients who were monitored with preoperative NIRS (NIRS group). Patient characteristics are given in Table 1. Gestational age, birth weight, prenatal diagnosis, and patient origin (inborn versus transport from another facility) were similar between groups. Mechanical respiratory support upon admission for the cohort was similar between groups (47% versus 42%, p 0.7). Inotropic score after the first hour of admission was higher in the control group ( versus ) and approached statistical significance (p 0.059). Fig 1. Respiratory variables in patients with near-infrared spectroscopy (NIRS) monitoring (dashed line) and without NIRS monitoring (solid line). The NIRS-monitored patients generally had higher SaO 2 and PaO 2, and lower PaCO 2, owing to lower use of mechanical ventilation and less restrictive inspired gas management. (FiO 2 fraction of inspired oxygen.) Preoperative Support Preoperative monitored data and cardiorespiratory support are shown in Table 2. Mechanical ventilation at any time during the preoperative period (39 of 47 versus 27 of 45 patients, p 0.014) and on the day of surgery (37 of 47 versus 23 of 45 patients, p 0.005) was more common in the control group compared with the NIRS group. Each group had a small number of patients who were extubated before surgery, accounting for the decrease in intubated patients on the day of surgery. Reasons for intubation were categorized as follows: cyanosis from a highly restrictive atrial shunt, presumed

4 574 JOHNSON ET AL Ann Thorac Surg PREOPERATIVE NIRS IN HLHS 2009;87:571 9 Table 4. Subanalysis by Near-Infrared Spectroscopy (NIRS) Availability Over Time Group 1 (Patient Nos. 1 35) Group 2 (Patient Nos ) Group 3 (Patient Nos ) p Value NIRS, n (%) 0 8 (40%) 37 (100%) Intubated ever, n (%) 31 (89) 15 (75) 20 (54) Intubated day of surgery, n (%) 30 (86) 14 (70) 16 (43) Intubation duration for intubated patients, hours Median (range) 80 (16 154) 89 (38 160) 68 (4 208) Mean SD Intubation duration for cohort, hours a Median (range) 72 (0 154) a 77 (0 160) b 23 (0 208) b Mean SD Carbon dioxide use, n (%) 0 2 (10) 0 Nitrogen use, n (%) 26 (74) 12 (60) 2 (5) a p value for comparison of Groups 1 and 3. b p value for comparison of Groups 2 and 3. circulatory mismatch defined as high arterial saturation without evidence of systemic hypoperfusion, shock with biochemical evidence, apnea, respiratory distress due to suspected primary lung disease, or elective because of diagnosis or the need for interhospital transport. Table 3 depicts the distribution of reasons for intubation between groups. Other than presumed circulatory mismatch, reasons for intubation were similar between groups. Intubation for presumed circulatory mismatch was more common in the control group compared with the NIRS group: 16 of 39 (41%) versus 5 of 27 (19%). Shock was the next most common reason for intubation in both groups. The median duration of intubation for patients receiving mechanical ventilation was 69 hours in the control group versus 36 hours in the NIRS group (p 0.099). Although carbon dioxide use was uncommon for this cohort, the use of nitrogen was significantly reduced in Fig 3. Hemodynamics in near-infrared spectroscopy (NIRS)-monitored patients, with (dashed line) and without (solid line) mechanical ventilation. Patients who were mechanically ventilated had lower diastolic and mean blood pressures (BP) despite lower SaO 2. (ns not significant.) Fig 4. Cerebral and somatic near-infrared spectroscopy (NIRS) measurements and regional oxygen extraction ratios (OER) in NIRSmonitored patients. Mechanical ventilation resulted in differential effects on regional blood flow: cerebral oxygenation and flow was increased, and somatic oxygenation and flow was decreased, in patients managed with mechanical ventilation. (rso 2 oxyhemoglobin saturation.)

5 Ann Thorac Surg JOHNSON ET AL 2009;87:571 9 PREOPERATIVE NIRS IN HLHS 575 Fig 5. Distribution of patients at incremental levels of ventilation charges. More patients in the nearinfrared spectroscopy (NIRS) group had zero charges for ventilation as compared with the control group. the NIRS group (70% versus 16%, p 0.001). Accordingly, the fraction of inspired oxygen (FiO 2 ) was greater in the NIRS group ( versus , p 0.008) as was the SaO 2 (91.9% 4.2% versus in control group, p 0.001). Arterial saturation, partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, and FiO 2 trends are shown in Figure 1. Higher SaO 2 in the NIRS group was not associated with lower diastolic or mean blood pressure, more biochemical shock, or worsened renal function (Fig 2). Control and NIRS groups were further stratified by specific diagnosis (aortic atresia versus aortic stenosis), and a subanalysis of SaO 2 between anatomic variants was performed. Within the control group, mean SaO 2 for patients with aortic atresia compared with patients with aortic stenosis was 87.3% versus 88.9% respectively (p 0.44). Arterial saturations were also similar between anatomic diagnoses within the NIRS group: 91.1% versus 92.8% in patients with aortic atresia versus aortic stenosis (p 0.19). The deployment of NIRS as a preoperative monitor occurred over time, as described in Methods, and is divided into three eras: group 1 included 35 patients during a time when NIRS was not available for preoperative care; group 2 included 20 patients during an intermediate era when NIRS use was dependent on monitor availability, and 8 (40%) of these patients were monitored with NIRS; and group 3 included 35 patients in whom NIRS was considered standard monitoring at our institution for all patients. Differences in respiratory support by NIRS availability over time is shown in Table 4. Similar to data in Table 2, fewer patients with preoperative NIRS were intubated and were exposed to nitrogen less often. The median duration of ventilation (23 hours) was significantly reduced for the group with routine NIRS monitoring when compared with groups without NIRS (72 hours, p 0.003) or with sporadic NIRS use (77 hours, p 0.049). Adjunctive therapy used more commonly in the NIRS group included caffeine as a respiratory stimulant (0% versus 38%, p 0.001) and milrinone (0% versus 9%, p 0.023). Serum creatinine, a surrogate measure of renal function, was lower in the NIRS group ( versus , p 0.023). The physiologic effects of controlled ventilation are shown in Figures 3 and 4. Patients who were mechanically ventilation had higher blood pressure and lower arterial saturation, but no difference in creatinine. The cerebral rso 2 was slightly higher, and the cerebral oxygen extraction ratio slightly lower, in mechanically ventilated patients, but was unchanged close to surgery. The somatic saturation was lower, and somatic oxygen extraction ratio higher, in mechanically ventilated patients. Operative Data Surgical data for the two groups is shown in Table 1. Age at surgery was similar between groups: days in the control group versus days in the NIRS group (p 0.3). Provision for pulmonary blood flow at stage 1 palliation differed between groups. A modified Blalock- Taussig shunt was placed in 45 of 47 patients (96%) in the control group and in 22 of 45 patients (49%) in the NIRS group (p 0.001) A right ventricle to pulmonary artery conduit was placed in the remainder of patients. Early (30-day) and intermediate (1-year) survival was 96% and 89%, respectively, for both groups. Resource Utilization The median duration of preoperative ventilaton (including patients with zero hours) was 69 hours (interquartile range, 38 to 90) in the control group, and was reduced by 48% to 36 hours (interquartile range, 0 to 90) in the NIRS group. Application of 2006 ventilation charge data revealed a concurrent 31% decrease in estimated ventilation charges for the NIRS group. The histogram in Figure 5 shows the distribution of patients at incremental levels of ventilation charges. More patients in the NIRS group had zero charges for ventilation as compared with the control group: 8 of 47 (17%) versus 22 of 45 (49%), respectively (p 0.002).

6 576 JOHNSON ET AL Ann Thorac Surg PREOPERATIVE NIRS IN HLHS 2009;87:571 9 Comment The neonate with HLHS has similar risk factors for circulatory failure before and after initial palliation with the Norwood operation. Oxygen delivery is usually progressively compromised during the preoperative period owing to falling pulmonary vascular resistance during the first hours to days of life and unrestricted blood flow through the ductus arteriosus. The use of arterial saturation as an index of pulmonary/systemic balance is confounded by the potential for pulmonary venous desaturation at low FiO 2 [7] and progressive systemic venous desaturation as the pulmonary to systemic blood flow ratio rises [1]. Optimization of systemic oxygen delivery as a perioperative management strategy, specifically with venous side saturation as a primary target, has been associated with low early mortality [8 10] and improved outcomes [3, 11]. Near-infrared spectroscopy gives a noninvasive estimate of regional venous saturation, which can be used like venous oximetry to monitor oxygen supply-demand relationships [5]. At Children s Hospital of Wisconsin, NIRS is routinely employed to monitor all preoperative neonates with HLHS. This study demonstrates beneficial reduction in the use of mechanical ventilation, inspired gases, and their associated charges with no impact on mortality or hospital length of stay concomitant with the introduction of NIRS for preoperative care. Traditional management of the preoperative neonate with HLHS has commonly employed endotracheal intubation, mechanical ventilation, and medical gas manipulation to increase pulmonary vascular resistance with the ultimate goal of augmenting systemic oxygen delivery through balancing pulmonary and systemic blood flow [12]. In a recent investigation of perioperative practices, 30% of centers surveyed reported use of preoperative controlled ventilation or inspired gases, or both, for patients with high arterial saturations without significant metabolic derangements [13]. Animal models and clinical experience have demonstrated the effectiveness of inspired CO 2 and subatmospheric FiO 2 on increasing pulmonary vascular resistance to increase systemic flow [14 16]. In anesthetized preoperative human neonates, controlled ventilation with either hypoxic gas mixture or inspired carbon dioxide reduces SaO 2 and the pulmonary to systemic flow ratio, but only hypercarbia improved systemic venous saturation [17]. The authors stated that they could not differentiate primary cerebral vasodilation from a more generalized improvement in systemic oxygen delivery. Our findings suggest that the primary effect of controlled ventilation with hypercarbia is on the cerebral circulation, and shows the utility of two-site NIRS in detecting changes in the regional distribution of blood flow. In contrast to the short-term effects of medical gas management on hemodynamics, the long-term benefit of routine mechanical ventilation or prolonged inspired gas therapy for the preoperative patient with HLHS is not established. In fact, mechanical ventilation in the preoperative patient with HLHS has been associated with more infection, more labile preoperative hemodynamics, and increased mortality [18, 19]. Without knowledge of venous oximetry or tissue oxygenation, the effect of any intervention on systemic oxygenation remains difficult to assess. Near-infrared spectroscopy monitoring of tissue oxygen delivery can aid management of the critically ill patient with vulnerable physiology. The Somanetics implementation of NIRS measures a venous weighted oxyhemoglobin saturation in tissue 2 to 3 cm under the probe and has been used to monitor oxyhemoglobin saturation in various tissue beds [5, 20]. This has been shown to be useful in monitoring tissue beds under autoregulatory (cerebral) and autonomic (somatic/renal) control. Recent data from our group have confirmed the clinical utility of NIRS as a real-time monitoring tool for early diagnosis and guided intervention of shock in critically ill patients and in patients after stage 1 palliation for HLHS [21, 22]. Additional evidence of NIRS utility is illustrated in this study. An evolution of practice to goal-directed therapy using tissue oximetry led to fewer invasive therapies in the current era. The median duration of intubation with routine use of NIRS was reduced to 23 hours as compared with more than 70 hours in the earlier groups (p 0.05), with a clinically relevant reduction in charges associated with mechanical ventilation. Additional charges not factored into this resource utilization analysis include those associated with administered medications, diagnostic studies, personnel, and potential ventilatorassociated complications. Noninclusion of charges associated with mechanical ventilation in this study likely underestimates the impact of NIRS on resource utilization. In conclusion, because high arterial saturation in the patient with HLHS may be harbinger of pulmonary overcirculation followed by circulatory shock, mechanical ventilation and other invasive therapies may be initiated without known effect. This study highlights the importance of continuous, noninvasive, real-time tissue oxygen saturation monitoring in guiding more appropriate interventions: use of two-site NIRS permits a safe reduction in the use of invasive therapies with equal or better outcome. Although limited by the observational design of historical cohorts, this study demonstrates how diffusion of innovative technology can facilitate reduction in invasive care with equal or better outcomes. When our study findings are viewed from a quality, safety, and outcomes perspective, the use of NIRS as a preoperative monitor takes on greater importance. Defects in patient care can be viewed as misuse, underuse, or overuse. Therapies viewed as standard of care from a traditional perspective preoperative mechanical ventilation and inspired gases can be viewed as overuse defects in the face of innovation, NIRS, as evidenced by the observed decrease in cost without a change in short- or intermediate-term outcomes.

7 Ann Thorac Surg JOHNSON ET AL 2009;87:571 9 PREOPERATIVE NIRS IN HLHS 577 The authors acknowledge Melodee Nugent of Quantitative Health Sciences in the Department of Pediatrics, Hua Liu, MS, Marilouise Anderson, BS, CTM, RHIA, and Evelyn Kuhn, PhD, of the Outcomes Department, Children s Hospital of Wisconsin, and Catherine Gedeit and Sarah Tweddell. References 1. Hoffman GM, Tweddell JS, Ghanayem NS, et al. Alteration of the critical arteriovenous oxygen saturation relationship by sustained afterload reduction after the Norwood procedure. J Thorac Cardiovasc Surg 2004;127: Hoffman GM, Ghanayem NS, Kampine JM, et al. Venous saturation and the anaerobic threshold in neonates after the Norwood procedure for hypoplastic left heart syndrome. Ann Thorac Surg 2000;70: Tweddell JS, Ghanayem NS, Mussatto KA, et al. Mixed venous oxygen saturation monitoring after stage 1 palliation for hypoplastic left heart syndrome. Ann Thorac Surg 2007; 84: Hoffman GM, Stuth EA, Jaquiss RD, et al. Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion. J Thorac Cardiovasc Surg 2004; 127: Hoffman GM, Ghanayem NS, Tweddell JS. Noninvasive assessment of cardiac output. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005: Tchervenkov CI, Jacobs JP, Weinberg PM, et al. The nomenclature, definition and classification of hypoplastic left heart syndrome. Cardiol Young 2006;16: Taeed R, Schwartz SM, Pearl JM, et al. Unrecognized pulmonary venous desaturation early after Norwood palliation confounds Qp:Qs assessment and compromises oxygen delivery. Circulation 2001;103: Tweddell JS, Hoffman GM, Fedderly RT, et al. Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure. Ann Thorac Surg 1999;67: Tweddell JS, Hoffman GM. Postoperative management in patients with complex congenital heart disease. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2002;5: Wright GE, Crowley DC, Charpie JR, et al. High systemic vascular resistance and sudden cardiovascular collapse in recovering Norwood patients. Ann Thorac Surg 2004; 77: Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: lessons learned from 115 consecutive patients. Circulation 2002;106(Suppl 1): Jobes DR, Nicolson SC, Steven JM, et al. Carbon dioxide prevents pulmonary overcirculation in hypoplastic left heart syndrome. Ann Thorac Surg 1992;54: Wernovsky G, Ghanayem N, Ohye RG, et al. Hypoplastic left heart syndrome: consensus and controversies in Cardiol Young 2007;17(Suppl 2): Mora GA, Pizarro C, Jacobs ML, et al. Experimental model of single ventricle: influence of carbon dioxide on pulmonary vascular dynamics. Circulation 1994;90: Riordan CJ, Randsbeck F, Storey JH, et al. Effects of oxygen, positive end-expiratory pressure, and carbon dioxide on oxygen delivery in an animal model of the univentricular heart. J Thorac Cardiovasc Surg 1996;112: Shime N, Hashimoto S, Hiramatsu N, et al. Hypoxic gas therapy using nitrogen in the preoperative management of neonates with hypoplastic left heart syndrome. Pediatr Crit Care Med 2000;1: Tabbutt S, Ramamoorthy C, Montenegro LM, et al. Impact of inspired gas mixtures on preoperative infants with hypoplastic left heart syndrome during controlled ventilation. Circulation 2001;104: Stieh J, Fischer G, Scheewe J, et al. Impact of preoperative treatment strategies on the early perioperative outcomes in neonates with hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 2006;131: Simsic JM, Kanter KR, Kirshbom PM. Does preoperative mechanical ventilation affect outcomes in neonates undergoing cardiac surgery? Cardiol Young 2007;17: Pigula FA, Gandhi SK, Siewers RD, et al. Regional low-flow perfusion provides somatic circulatory support during neonatal aortic arch surgery. Ann Thorac Surg 2001;72: Hoffman GM, Ghanayem NS, Berens RJ, et al. Reduction in critical indicators of shock by routine use of two-site NIRS in pediatric ICU patients [Abstract]. Anesthesiology 2006;105: A Hoffman GM, Ghanayem NS, Mussatto KA, et al. Postoperative two-site NIRS predicts complications and mortality after stage 1 palliation of HLHS [Abstract]. Anesthesiology 2007;107:A234. DISCUSSION DR PETROS ANAGNOSTOPOULOS (Phoenix, AZ): What would you do if you had high saturations, good infrared spectroscopy, but evidence of acidosis either by lactate or by development of base deficit in a preoperative patient? DR JOHNSON: What would I do if the NIRS numbers were okay and the other indicators were not okay? DR ANAGNOSTOPOULOS: Yes. DR JOHNSON: If the NIRS values are reassuring but blood gas analysis reveals acidosis, we investigate other causes of acidosis. Specifically, we would measure electrolytes, venous saturation and lactate. The most common cause of acidosis we find in our patients is a hyponatremic hyperchloremic metabolic acidosis. In the face of elevated serum chloride and signs of good tissue perfusion, we tolerate a moderate base deficit on blood gas analysis. In our experience, systemic hypoperfusion is identified early with NIRS and the development of lactic acidosis usually follows if there is delayed intervention. The scenario of high regional oximetry can occur during a shock state, but usually is due to distributive shock. As a result, NIRS data is not the only indicator that we use to monitor for hypoperfusion, but continue to follow conventional clinical and laboratory indicators of shock. DR JEFF L. MYERS (Boston, MA): I noticed when you divided your NIRS patients into intubated and nonintubated, you essentially showed that the cerebral NIRS were maintained and there s a trend toward the somatic NIRS going down. And you didn t really go into your management strategy very much, but it seems like you essentially ignored the peripheral saturations if the cerebral NIRS are okay? And then if that s the strategy, you know, when we look at cerebral NIRS that are maintained and somatic NIRS that fall, to us that means we re in a low cardiac output state. We re shunting away from somatic beds and muscle beds. And so do you find is that a trend, or not? If you maintain cerebral NIRS and your somatic falls, that these are indeed patients that are developing a lactic acidosis and acidemia, or not?

8 578 JOHNSON ET AL Ann Thorac Surg PREOPERATIVE NIRS IN HLHS 2009;87:571 9 DR JOHNSON: We would expect cerebral saturations to be less labile in early shock states than somatic saturations due to cerebral autoregulation and as a result, we were not surprised by maintained cerebral saturations in the presence of falling somatic saturations. If there is evidence of hypoperfusion, we generally will see a decline in somatic saturation well before we see a fall in cerebral saturation. When we use NIRS monitoring, the focus isn t necessarily on absolute tissue oxyhemoglobin levels, but rather on differences between the arterial and regional oximetry data. The typical scenario in the patient who is showing early evidence of systemic hypoperfusion, arterial saturations might not be much different from baseline and arterialcerebral saturation gradient will be maintained, but the arterialsomatic gradient will widen. The management strategy at this point would be determined after assessing other data such as central venous pressure, mean arterial blood pressure, physical examination, and hemoglobin. Therapies we generally employ in these situations might be volume administration, milrinone, packed red blood cells, lasix, or low-dose morphine. Usually these maneuvers are effective and less commonly is intubation necessary. In the intubated population, the lower somatic saturation in the presence of maintained cerebral saturations can reflect increased systemic vascular resistance from the discomfort of having an endotracheal tube in place or intentional hypercarbic management strategy that alters distribution or shunting of blood flow, and does not necessarily indicate low cardiac output. Although somatic saturations fell as patients approached their surgery dates, the arterial-somatic saturation gradient we observed was not associated with a progressive lactic acidosis from low cardiac output. DR JOSEPH M. FORBESS (Dallas, TX): I wanted to ask you a question that struck me. I mean, I think I ve got the answer to it, but I m curious what your thoughts are. When you say goaldirected therapy, what you re really getting at is goal-directed benign neglect here. And so why is it that a preoperative hypoplast, in your mind, who has a blood pressure of 53/22 mm Hf, before we ve done anything to him, on no inotropes, has NIRS that are typically fine, like you re saying here, and if we were looking at those same old-fashioned vital signs postoperatively, excluding NIRS as a vital sign, things would look so profoundly different? I ll even add that in a preoperative patient with those old-fashioned vital signs, the echocardiograph shows torrential pulmonary vein return. What s the difference between those 2 patients, the preoperative and the postoperative patient, in your mind? DR JOHNSON: You re asking why the NIRS values are so different preoperatively as compared with postoperatively when the other vital signs are similar? DR FORBESS: I m saying if we re looking postoperatively at a patient that has a blood pressure of 53/22 mm Hg, their NIRS are in fact not going to be like the preoperative patient. And so there is some difference between these 2 patients. This is torrential pulmonary blood flow we re seeing preoperatively. The Qp:Qs is far from optimized preoperatively. So why do you think those 2 patients are perfusing their brains so differently? DR JOHNSON: Well, I think the difference in values that you described would be due largely to the fact that the postoperative patient has experienced surgery and cardiopulmonary bypass and has an overall lower cardiac output as compared with the preoperative patient. With diminished cardiac output, arterial blood pressure can be maintained due to alterations in systemic vascular resistance with a simultaneous decrease in systemic perfusion and therefore decreased somatic NIRS values. DR FORBESS: I think this paper is wonderful. I m going to take it home and make the case, as I try to, that I think we underestimate how profoundly we impact the ability for the pump to do its job. And we can look at these vital signs preoperatively and everything seems to be okay. And I agree that intubating a child because they ve got a blood pressure of even 50/19 mm Hg, when they ve got cerebral NIRS of 68%, is probably something we ought to think about. DR JAMES S. TWEDDELL (Milwaukee, WI): I think the answer to your question is that the total cardiac output is severely limited in the postoperative patient due to ischemia-reperfusion injury with endothelial dysfunction, diastolic dysfunction and occasionally systolic dysfunction. If the patient has a high Qp/Qs preoperatively, but can generate a large cardiac output, then oxygen delivery is maintained. Postoperatively with a decreased cardiac output much more precise partitioning is required. The postoperative patient is living on the razor s edge. DR PIROOZ EGHTESADY (Cincinnati, OH): Were there any category of patients that you saw that if one had looked at the saturations, one would have a false sense of reassurance because the saturations looked okay ie, sats in the high 70s to low 80s but the NIRS, in fact, when you put it on, say, would say we re in trouble, NIRS in the 40s or 50s? Was there a particular subtype of patients who you found that would have been potentially picked up as being in trouble that would have been missed otherwise had you not put the NIRS on? DR JOHNSON: Did we find a group of patients where the arterial saturations were inappropriately reassuring? DR EGHTESADY: I meant that the arterial saturations, you would think, oh, this baby s balance was okay. But it s not, in fact, because when you put the NIRS on, you would see the values were low. Or were the majority of their NIRS perfectly fine preoperatively? DR JOHNSON: So you re describing the patient with arterial saturations in the 80s to low 90s? DR EGHTESADY: Say the saturations were in the 80s, but then when you put the NIRS on, it s like in the 40s or 50s or something that would make you say, wait a second, this kid is not ok. DR CARL L. BACKER (Chicago, IL): I think I also think Nancy is going to come up that is exactly the patient in which I find NIRS monitoring so useful. The blood pressure is fine, the heart rate is fine, the peripheral arterial saturation is 85%, and the renal NIRS is dropping, dropping, dropping. And then hours later the patient has an arrest or has to go on extracorporeal membrane oxgenation because you didn t recognize the early warning signs. Nancy, go ahead, you re the expert. DR GHANAYEM: Doctor Johnson is correct in the observation that arterial saturations are usually higher than the 70s to low 80s. In this series, the mean arterial saturation was in the low 90s during the preoperative period. The scenario presented with regard to lower arterial saturations does occur, but infrequently and typically does so with impaired regional oximetry. In gen-

9 Ann Thorac Surg JOHNSON ET AL 2009;87:571 9 PREOPERATIVE NIRS IN HLHS 579 eral, the patient with low arterial saturation is more labile and has increased work of breathing usually due to pulmonary pathology from edema or atelectasis that likely leads to pulmonary venous desaturation. This scenario is often associated with increased systemic vascular resistance and compromised systemic perfusion. Whereas in the past, we might have been satisfied with preoperative arterial saturations of 75% to 85%, we now find this level of desaturation concerning usually because there is concomitant regional tissue hypoxia as detected with NIRS. Similar to our previous published postoperative data on mixed venous oximetry, two-site NIRS monitoring has unmasked the false reassurance that arterial saturation are optimal for oxygen delivery if they are 75% to 85%. With two-site NIRS, we are able to identify regional tissue hypoxia even in the patient who might have the ideal arterial saturation of 80%, and intervene before metabolic derangements or circulatory collapse occurs. DR BACKER: Let s take a quick show of hands here. We did this a year or two ago and not many people were using it. But now, how many people are using the NIRS monitoring routinely in their postoperative patients? And how many people are not using it? It looks like 60% to 70% yes, 30% to 40% no. Definitely the majority are now using NIRS monitoring routinely. DR FORBESS: How many have it in every bed in their intensive care unit and use it? DR BACKER: That s this half of the room, it looks like. DR FORBESS: Cathetherization laboratory? DR BACKER: A few hands. Operating room? A lot more hands. Thoracic Surgery Foundation for Research and Education Turning Today s Research Into Tomorrow s Patient Care Our patients don t follow the details of our research. They don t discuss unexpected breakthroughs or technical setbacks. They are not always aware of how changes in health care policies impact research funding and lab time. Nonetheless, the advances we make in thoracic surgery touch each and every one of them. New surgical techniques and potent new drugs improve patient health and extend patient lives. That is an outcome everyone can understand, and it s the one that has continued to push the Thoracic Surgery Foundation for Research and Education (TSFRE) forward since its inception in TSFRE was founded by the four major thoracic surgery organizations: the American Association for Thoracic Surgery (AATS), The Society of Thoracic Surgeons (STS), the Southern Thoracic Surgical Association (STSA), and the Western Thoracic Surgical Association (WTSA). As it was 16 years ago, the Foundation s mission is to support research and education in thoracic surgery. The Foundation, however, has not only maintained its position as a leading supporter of research and education, it has also expanded its reach. Over the past few years, the Foundation has established a comprehensive development program, improved its public policy training opportunities for surgeons, and partnered with other foundations such as the LUNGevity Foundation to improve support for research training. Perhaps most importantly, the Foundation has chosen to play a leading role in changing the current training paradigm for thoracic surgeons by becoming a founding organization of the Joint Council on Thoracic Surgery Education (JCTSE). Along with the AATS, the American Board of Thoracic Surgery (ABTS), and the STS, TSFRE has committed its resources to support and empower the JCTSE to overhaul the current thoracic surgery training program and coordinate all thoracic surgery education in the United States. TSFRE is a pivotal force for the growth and vitality of our specialty and its role is increasing, particularly in the areas of research, academic career development, and postgraduate education. The philanthropic participatory index for members of the Foundation s founding organizations is important as these surgeons know that giving begins at home and TSFRE is their home for research and education. Foundation supporters through donations or networking can have a significant impact on the future of cardiothoracic surgery and the welfare of our patients. If you would like to make a pledge or receive more information about giving to TSFRE, please visit www. TSFRE.org or call Donna Kohli, TSFRE Executive Director at by The Society of Thoracic Surgeons Ann Thorac Surg 2009;87: /09/$36.00 Published by Elsevier Inc