Introduction: Routine hemodynamic parameters have largely been used to help guide clinical management after the Norwood operation. Changes in these parameters that indicate increased risk of cardiac arrest or death have not been well delineated and rather age population normal are frequently applied to this unique patient population. This study aimed to compare conventional hemodynamics parameters in children with parallel circulation in the 48 hours prior to discharge or death.

Methods: This was a retrospective study including patients after the Norwood operation. By virtue, all these patients had parallel circulation. Blood pressure, respiratory rate, heart rate, arterial saturation by pulse oximetry, shock index, cerebral near infrared spectroscopy, and renal near infrared spectroscopy were collected in the 48 hours immediately preceding either discharge home or death.

Results: Heart rate was significantly higher at multiple time points leading up to death in non-survivors, and significantly lower the hour before death. Systolic blood pressure was significantly lower in non-survivors 48 hours prior to discharge but not at any other timepoint. Respiratory rate was significantly lower in non-survivors. Arterial saturation by pulse oximetry was significantly lower in non-survivors. Shock index was significantly higher in non-survivors at multiple time points prior to death. Cerebral near infrared spectroscopy was significantly lower in non-survivors at multiple time points prior to death. Renal near infrared spectroscopy was significantly lower in non-survivors at multiple time points prior to death. Near infrared spectroscopy was most consistently altered in the hours immediately preceding death.

Conclusion: Conventional hemodynamic monitoring patterns can help facilitate identification of those at risk for death. However, changes are subtle and present in only a few parameters. Near infrared spectroscopy changes more dramatically in non-survivors and may better identify individuals at risk of death.

Keywords: Norwood operation, single ventricle, functionally univentricular, mortality, cardiac arrest, hemodynamic parameters, near infrared spectroscopy

Despite improvements in the outcomes of patients who undergo the Norwood operation, early survival is still comparatively lower when compared to other cardiac defects that require surgical repair in the neonatal period. Risk factors found to be associated with postoperative mortality include low birth weight, genetic abnormalities, restrictive atrial septum, history of obstructed total anomalous pulmonary venous connection, and tricuspid valve regurgitation.¹

Close monitoring of all postoperative patients is necessary, but hemodynamic monitoring is particularly important in the higher risk post-Norwood population. Monitoring of heart rate, blood pressure, respiratory rate, and pulse oximetry have been the routine in clinical use. However, specific evidence for the utility of these parameters in the post-Norwood population is scarce. Changes in these parameters that are consistent with cardiorespiratory instability and increased risk of mortality have not been well described with some data even demonstrating the limitations of these hemodynamic indices.² Rather, population normal values for this specific age range are routinely applied to these patients who have circulations that are vastly different from those included in the studies that determined the age-appropriate populations normal values. Application of age-matched normal values from patients with fully septated, biventricular circulation may not yield the same diagnostic yield or indicate the same underlying physiologic changes.

The primary aim of this study was to determine the association of hemodynamic parameters easily visible on routine clinical monitoring with inpatient mortality in patients after a Norwood operation.

Study design and patient identification

This study was a single-center, retrospective study. Children who underwent a Norwood operation between January 2011 and January 2021 were identified using our institutional cardiothoracic surgery database. Patients who survived for at least 48 hours after the Norwood were included. Those who died within the first 48 hours after the Norwood were excluded. Patients who remained inpatient until the Glenn operation were also excluded from this study as were patients who went on to cardiac transplant in the interstage period.

Those who survived to discharge will be referred to as “survivors” in this manuscript while those who did not survive to discharge will be referred to as “non-survivors”. “Mortality” in this manuscript refers to inpatient mortality unless otherwise specified.

Hemodynamic parameters

The premise of the study was to focus on routine hemodynamic parameters which appear on easily visible screens for inpatients. This included heart rate in beats per minute, systolic blood pressure in mmHg, diastolic blood pressure in mmHg, respiratory rate in breaths per minute, arterial saturation by pulse oximetry (%), cerebral near infrared spectroscopy, and renal near infrared spectroscopy. Of note, cerebral near infrared spectroscopy and renal near infrared spectroscopy was only available for the non-survivors as renal near infrared spectroscopy is no longer followed 48 hours prior to discharge in those who survive to discharge.

The following calculated parameters were included in this study: shock index and oxygen extraction ratio. Shock index was calculated as heart rate divided by the systolic blood pressure. Oxygen extraction ratio was calculated as the (arterial saturation by pulse oximetry – renal near infrared spectroscopy) / (arterial saturation by pulse oximetry x 100). These two parameters were included in this study, despite not meeting the premise of being a parameter displayed on clinical monitors, as they are easily calculable using parameters displayed on clinical monitors.

Time points

The 48 hours preceding death or discharge compromised the time-period of interest. The hemodynamic parameters mentioned above were collected at the following timepoints: 48 hours prior to death or discharge, 36 hours prior to death or discharge, 24 hours prior to death or discharge, 12 hours prior to death or discharge, 8 hours prior to death or discharge, 4 hours prior to death or discharge, 3 hours prior to death or discharge, 2 hours prior to death or discharge, and 1 hour prior to death or discharge.

Statistical analyses

Continuous variables are presented as the mean and standard deviation while descriptive variables are presented as the absolute frequency and the percentage.

Values for each specific hemodynamic parameter at each time point were compared between survivors and non-survivors using a independent means T-test due to the normalcy of distribution.

Next, a series of paired T-tests were conducted to compare the values for each specific hemodynamic parameter to the value at 48 hours prior to death or discharge. After this, a series of paired T-tests were conducted to compare the values for each specified hemodynamic parameter to the value at the time point immediately preceding it.

All statistical analyses were conducted using SPSS Version 23.0. A p-value of less than 0.05 was considered statistically significant. Any use of “significantly” or “significant” refers to statistical significance unless otherwise specified.

Cohort characteristics

A total of 110 patients were included in the final analyses. A total of five (4.5%) patients who met inclusion criteria experienced inpatient mortality. The principle cardiac diagnoses are listed in Table 1. The most frequent diagnosis was hypoplastic left heart syndrome in 73 (66.3%). The median age at death or discharge was 47.5 days.

Heart rate

Heart rate was significantly different between survivors and non-survivors at multiple time points with non-survivors having significantly higher heart rates at 8 hours, 4 hours, 3 hours, and 2 hours prior to death or discharge. At one hour prior to discharge non-survivors had a statistically significantly lower heart rate (Table 2).

When only non-survivors were analyzed, there was significant decrease (21.9%) in heart rate from 48 hours prior to death or discharge to 1 hour prior to death or discharge (Table 2).

Systolic blood pressure

Systolic blood pressure was significantly lower in non-survivors when compared to survivors at 48 hours and 1 hour prior to death or discharge.

When only non-survivors were analyzed, there were no significant differences in systolic blood pressure between timepoints.

Diastolic blood pressure

There were no significant differences in diastolic blood pressure between survivors and non-survivors.

When only non-survivors were analyzed, there were no significant differences in diastolic blood pressure between timepoints.

Respiratory rate

Respiratory rate was significantly different between survivors and non-survivors at multiple time points. Non-survivors had a significantly lower respiratory rate at 48 hours, 36 hours, 24 hours, 12 hours, 8 hours, 4 hours, 3 hours, and 1 hour prior to death or discharge.

When only non-survivors were analyzed, there were some significant differences within timepoints but not at any timepoint when compared to 48 hours prior to death or discharge.

Arterial saturation by pulse oximetry

Arterial saturation by pulse oximetry was significantly lower in non-survivors at 48 hours, 12 hours, 4 hours, and 1 hour prior to death or discharge.

When only non-survivors were analyzed, there were some significant changes within timepoints but not at any timepoint when compared to 48 hours prior to death or discharge.

Shock index

Shock index was significantly different between survivors and non-survivors at multiple timepoints. Shock index was significantly higher in non-survivors at 48 hours, 36 hours, 4 hours, 3 hours, and 1 hour prior to death or discharge.

When only non-survivors were analyzed, there were some significant differences within timepoints but not at any timepoint when compared to 48 hours prior to death or discharge.

Cerebral near infrared spectroscopy

When only non-survivors were analyzed, there were some significant differences between timepoints when compared to 48 hours prior to death or discharge. Cerebral near infrared spectroscopy values were lower in non-survivors at 24 hours, 3 hours, and 1 hour prior to death or discharge when compared to 48 hours prior to death or discharge. There was a 21.3% decrease in cerebral near infrared spectroscopy from 48 hours to 1 hour prior to death.

Renal near infrared spectroscopy

When only non-survivors were analyzed, there were some significant differences between timepoints when compared to 48 hours prior to death or discharge. Renal near infrared spectroscopy values were lower in non-survivors at 24 hours, 3 hours, 2 hours, and 1 hour prior to death or discharge when compared to 48 hours prior to death or discharge. There was an 18.7% decrease in renal near infrared spectroscopy noted from 48 hours to 1 hour prior to death.

Oxygen extraction ratio

When only non-survivors were analyzed, there were some significant differences between timepoints when compared to 48 hours prior to death or discharge. Oxygen extraction ratio was higher in non-survivors at 24 hours, 3 hours, 2 hours, and 1 hour prior to discharge. There was a 34.2% increase in oxygen extraction ratio noted from 48 hours to 1 hour prior to death.

These analyses demonstrate that heart rate, systolic blood pressure, respiratory rate, arterial saturation by pulse oximetry, shock index differ at some point in the 48 hours prior to death or discharge in Norwood admissions between survivors and non-survivors. Also, importantly, when only non-survivors were considered, significant changes in heart rate, cerebral near infrared spectroscopy, renal near infrared spectroscopy, and oxygen extraction ratio were found from 48 hours prior to death or discharge to 1 hour prior to death or charge.

Cerebral near infrared spectroscopy and renal infrared spectroscopy allow for the noninvasive estimation and trending of venous saturation, thus facilitating continuous monitoring of the balance of systemic oxygen supply and demand. This study demonstrates that these metrics significantly change most consistently before death during the Norwood admission. Moreover, the changes are more noticeable and significant than other more conventional vital signs that are monitored such as blood pressure and heart rate.

These findings should not be truly surprising. Human life is dependent on adequate systemic oxygen delivery with the adequacy of systemic oxygen delivery being the result of a balance between systemic oxygen delivery and systemic oxygen consumption. Other factors such as heart rate, blood pressure, stroke volume, and hemoglobin are simply components that may modulate systemic oxygen delivery. It must be kept in mind, however, that these are not direct indicators of the adequacy of systemic oxygen delivery.² Medical management and therapy should be titrated to maintaining systemic oxygen delivery. This becomes particularly important in the setting of parallel circulation as is noted after the Norwood operation, a stage in which following the venous saturation can be particularly helpful to mitigate morbidity and mortality.^2–9

Anecdotally, however, medical management in the inpatient clinical setting is often titrated to blood pressure and maintaining “normal” blood pressure values based on healthy children with fully septated, biventricular circulation. Maintenance of blood pressure may be accomplished by use of fluid boluses, vasoactive medications, and blood transfusions, all of which have associated risks of their own and may not consistently improve systemic oxygen delivery.^10–14 However, if the blood pressure is below “normal” but systemic oxygen delivery is adequate, augmentation of blood pressure and systemic vascular resistance is not likely lead to any improvement in systemic oxygen delivery, and in fact, may be detrimental. This is supported by current evidence that a low systemic vascular resistance state is the most stable state for those with parallel circulation. When coupled with a simultaneous high cardiac output state, favorable outcomes are maximized in these patients with low systemic vascular resistance.^9,15–20 This further highlights that simply increasing blood pressure and systemic vascular resistance are not what should be targeted as goals for titrating care.

A low cardiac output state may be compensated for by an increase in systemic vascular resistance to maintain mean arterial pressure, causing the oxygen demand of the heart to increase. Consequently, the balance between systemic oxygen delivery and consumption may be impaired. Current studies show that even with “normal” or slightly low blood pressure values, patients still suffered from cardiac arrest if cardiac output was significantly reduced. Additionally, a reduction in oxygen saturation minutes prior to cardiac arrest seemed to play an influential role in the deterioration of patients.²¹ This only further highlights the importance of adequate oxygen delivery to maximize outcomes in this patient population.

The combination of arterial and venous oximetry allows for an assessment of cardiac output. In fact, the Fick principle is based on this, with the arteriovenous oxygen difference being utilized in the denominator. In the current study, the isolated cerebral and renal near infrared spectroscopy values were utilized and modeled initially. Then, the oxygen extraction ratio was calculated. The oxygen extraction ratio as calculated for this study represents the arteriovenous difference as a proportion of the systemic saturation. This also significantly changed over time, increasing closer to the time of death. The near infrared spectroscopy was utilized as a surrogate marker for venous saturations as near infrared spectroscopy has been found to have good trend correlation with venous saturations obtained from the same region although the absolute correlation may be limited.²²

Regardless of how the near infrared spectroscopy data were utilized, in isolation or as part of the calculation of the oxygen extraction ratio, the near infrared spectroscopy data began significantly changing at three hours prior to death when compared to the 48 hours prior to death timepoint. This occurred for both the cerebral and renal near infrared spectroscopy, neither was necessarily more sensitive as an indicator than the other. This relates to the ongoing debate of the utility of superior versus inferior caval vein saturation for predicting a hemodynamic deterioration. The thought for many years had been that superior caval vein saturations are the most useful although data from those with parallel circulation were never truly analyzed to demonstrate this. Data now exists to demonstrate that both inferior and superior caval vein saturations can be helpful.⁶ The current study’s demonstration of the utility of both cerebral and near infrared spectroscopy, as surrogates of superior and inferior caval vein saturation, respectively, helps further solidify the clinical utility of both sites to monitor venous oximetry.

Undoubtedly, a criticism of this study will be that the study simply includes hemodynamic parameters that can be easily viewed on a monitor in the clinical setting. Interventions, including but not limited to, vasoactive medications and respiratory support, were not accounted for. This was to demonstrate what the utility of the hemodynamic parameters are in their rawest and purest form as indicators rather than trying to assess what the impact of interventions on these parameters is. The notion here being that most of these hemodynamic parameters should be treated as modifiable entities to help modulate systemic oxygen delivery but are not the target parameters themselves.

Most certainly the non-survivors were subject to several interventions in the 48-hour period of interest. The data here demonstrate that even though these interventions may have helped keep parameters such as heart rate, blood pressure, and arterial saturation by pulse oximetry consistent to the initial timepoint in the non-survivors that systemic oxygen delivery was not maintained simultaneously. This, in and of itself, is a very telling point.

While some may view the above as a limitation of this study, this is simply the purposeful nature of the study design in which to assess the hemodynamic parameters as representative indicators and not as modifiable targets.

Limitations of this study include the fact that this is a single-center study and thus the findings of this study may be influenced by tangible and intangible center-specific variables. Additionally, due to the single-center nature of this study, the frequency of mortality was relatively low. This does limit the statistical power, particularly for the independent samples T-test. The inherent nature of the paired T-tests conducted in the subset of non-survivors lends these subset analyses greater statistical power although, albeit, still relatively limited. Nonetheless, even despite this, significant differences were able to be detected.

Conventional hemodynamic monitoring patterns can help facilitate identification of those at risk for death. However, changes are subtle and present in only a few parameters. Near infrared spectroscopy changes more dramatically in non-survivors and may better identify individuals at risk of death.

None.

None.

Author declares that there are no conflicts of interest.

1. Chowdhury SM, Graham EM, Atz AM, et al. Validation of a simple score to determine risk of hospital mortality after the Norwood procedure. Semin Thorac Cardiovasc Surg. 2016;28(2):425–433.
2. Dhillon S, Yu X, Zhang G, et al. Clinical hemodynamic parameters do not accurately reflect systemic oxygen transport in neonates after the Norwood operation. Congenit Heart Dis. 2015;10(3):234–239.
3. Barnea O, Santamore WP, Rossi A, et al. Estimation of oxygen delivery in newborns with a univentricular circulation. Circulation. 1998;98(14):1407–1413.
4. Charpie JR, Dekeon MK, Goldberg CS, et al. Postoperative hemodynamics after Norwood palliation for hypoplastic left heart syndrome. Am J Cardiol. 2001;87(2):198–202.
5. Francis DP, Willson K, Thorne SA, et al. Oxygenation in patients with a functionally univentricular circulation and complete mixing of blood: are saturation and flow interchangeable? Circulation. 1999;100(21):2198–2203.
6. Dabal RJ, Rhodes LA, Borasino S, et al. Inferior vena cava oxygen saturation monitoring after the Norwood procedure. Ann Thorac Surg. 2013;95(6):2114–2120.
7. Hoffman GM, Ghanayem NS, Kampine JM, et al. Venous saturation and the anaerobic threshold in neonates after the Norwood operation for hypoplastic left heart syndrome. Ann Thorac Surg. 2000;70(5):1515–1520.
8. 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(4):1301–1310.
9. Tweddell JS, Hoffman GM, Fedderly RT, et al. Patients at risk for low systemic oxygen delivery after the Norwood procedure. Ann Thorac Surg. 2000;69(6):1893–1899.
10. Loomba RS, Flores S. Use of vasoactive agents in postoperative pediatric cardiac patients: Insights from a national database. Congenit Heart Dis. 2019;14(6):1176–1184.
11. Patel RD, Weld J, Flores S, et al. The acute effect of packed red blood cell transfusion in mechanically ventilated children after the Norwood operation. Pediatr Cardiol. 2022;43(2):401–406.
12. Savorgnan F, Bhat PN, Checchia PA, et al. RBC transfusion induced ST segment variability following the Norwood operation. Crit Care Explor. 2021;3(5):e0417.
13. Savorgnan F, Flores S, Loomba RS et al. Hemodynamic response to calcium chloride boluses in single-ventricle patients with parallel circulation. Pediatr Cardiol. 2022;43(3):554–560.
14. Li J, Zhang G, Holtby H, et al. Adverse effects of dopamine on systemic hemodynamic status and oxygen transport in neonates after the Norwood procedure. J Am Coll Cardiol. 2006;48(9):1859–1864.
15. Hoffman GM, Scott JP, Ghanayem NS, et al. Identification of time-dependent risks of hemodynamic states after stage 1 Norwood palliation. Ann Thorac Surg. 2020;109(1):155–162.
16. Hoffman GM, Niebler RA, Scott JP, et al. Interventions associated with treatment of low cardiac output following stage I Norwood palliation. Ann Thorac Surg. 2021;111(5):1620–1627.
17. Migliavacca F, Pennati G, Dubini G, et al. Modeling of the Norwood circulation: effects of shunt size, vascular resistances, and heart rate. Am J Physiol Heart Circ Physiol. 2001;280(5):H2076–2086.
18. De Oliveira NC, Ashburn DA, Khalid F, et al. Prevention of early sudden circulatory collapse after the Norwood operation. Circulation. 2004;110(11 Suppl 1):133–138.
19. Tweddell JS, Hoffman GM, Fedderly RT, et al. Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure. Ann Thorac Surg. 1999;67(1):161–167.
20. Lee B, Villarreal EG, Mossad EB, et al. Alpha-blockade during congenital heart surgery admissions: analysis from national database. Cardiol Young. 2021;32(7):1136–1142.
21. Erez E, Mazwi ML, Marquez AM, et al. Hemodynamic patterns before In hospital cardiac arrest in critically Ill children: an exploratory study. Crit Care Explor. 2021;3(6):e0443.
22. Loomba RS, Rausa J, Sheikholeslami D, et al. Correlation of near-infrared spectroscopy oximetry and corresponding venous oxygen saturations in children with congenital heart disease. Pediatr Cardiol. 2022;43(1):197–206.