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Ann Thorac Surg 2000;69:1229-1235
© 2000 The Society of Thoracic Surgeons

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ORIGINAL ARTICLES: CARDIOVASCULAR

Cerebral vascular effects of aortovenous cannulations for pediatric cardiopulmonary bypass

^a Division of Cardiovascular Surgery, Department of Surgery, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, K1H 8L1, Canada
^b Department of Anaesthesia, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada

Address reprint requests to Dr Rodriguez, Division of Cardiovascular Surgery, Department of Surgery, Children’s Hospital of Eastern Ontario, 401 Smyth, Ottawa, ON, K1H 8L1, Canada
e-mail: rodriguez{at}cheo.on.ca

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. The effects of aortovenous cannulations for pediatric cardiopulmonary bypass on cerebral blood flow velocity (CBFV) and electroencephalography (EEG) were evaluated.

Methods. CBFV and EEG were continuously recorded before (baseline), during, and after cannulations until initiation of cooling (mean ± 95% confidence interval). Vasopressors and/or volume replacement were administered if mean arterial pressure (MAP) decreased below 35 mm Hg. Cannulation-related EEG slowing was used as a criterion for electrocortical alteration.

Results. We studied 124 children (3 days to 17 years of age). Aortic and venous cannulations decreased mean CBFV by 10 ± 3% and 13 ± 4%, respectively, from baseline (p < 0.001). MAP diminished (p < 0.01) by 8 ± 3% and 12 ± 4%, respectively, from precannulation values (53 ± 2 mm Hg). Right atrial cannulation, which was often chosen because the patient was hemodynamically unstable, was more frequently associated with pharmacologic intervention when compared with superior vena cava (SVC) cannulation (p < 0.01). Transient EEG alterations (n = 20) were associated with persistently low MAP (< 30 mm Hg), low CBFV (< 69%), and aortic (n = 4) or SVC (n = 7) cannula malposition. Infants with right atrial cannulation and intervention had more frequent EEG alterations (p = 0.04). Patients requiring intervention were younger (p < 0.01) and had longer hospital stay (p < 0.01) than those without intervention.

Conclusions. Cerebral effects of cannulations are greater in young infants. This was found to be associated with low MAP during heart manipulation or consequence of cannula malpositions.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Institution of cardiopulmonary bypass (CPB) in children requires the insertion of an aortic cannula and one or two venous cannulae. Unsuccessful cannulation may lead to cerebral complications [1–3]. A malpositioned aortic cannula may obstruct cerebral blood flow, or it may cause a preferential flow into the descending aorta and "steal" blood flow from the brain’s circulation [1]. Alternatively, obstruction by the superior vena caval cannula may decrease cerebral venous drainage and potentially lead to brain dysfunction [2].

Transcranial Doppler (TCD) echography and electroencephalography (EEG) provide information regarding the status of the brain circulation and function during pediatric cardiac operations [2]. Although TCD measures the velocity of red blood cells rather than blood flow, the relative changes in the spectral characteristics of the flow velocity profile provide understanding of the functional status of the cerebral vasculature [3, 4]. The EEG describes the cerebrocortical activity and detects neuronal dysfunction due to cortical ischemia or hypoxia [5, 6].

The purpose of this study was to evaluate the cerebral effects of aortic and venous cannulations in infants and children undergoing open heart surgery. In this investigation, cerebral blood flow velocity (CBFV) and EEG were used as indicators of the changes in the cerebral circulation and function during these surgical maneuvers.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Transcranial Doppler
With parental consent and Institutional Ethics Review Board approval, children who had open heart surgery from April 1996 to December 1997 were studied. A 2-MHz pulsed-wave Doppler probe (Medasonics, Fremont, CA) was secured on the child’s temporal window before surgical incision. The signal was range-gated at different depths for consistent insonation of the right middle cerebral artery (sample volume: 7 mm; angle of 0°). After Doppler shift calculation, signals were computed using spectral analysis, and the instantaneous mean, peak, and end-diastolic CBFV were calculated over the last five cardiac cycles (high-pass filter: 150 Hz).

Baseline CBFV was measured under conditions of hemodynamic stability and before cannulation of the aorta. Thereafter, CBFV was recorded when the tip of either the arterial or venous cannula was inserted into the vascular lumen by the surgeon. A subsequent measurement was obtained 40 seconds after each maneuver. If a cannula was inserted under partial CPB, the CBFV was compared with its immediate precannulation values. Cannulations were identified as either aortic, right atrium, superior vena cava (SVC), or inferior vena cava (IVC).

Electroencephalography
Scalp-surface EEG activity was recorded (bandpass 1 to 70 Hz) through 10 bipolar derivations at frontocentral, centrooccipital, frontotemporal, and temporooccipital locations using a 16-channel Grass machine (Grass, Quincy, Mass). The EEG was recorded, interpreted in real-time in the operating room by one of the investigators, and verified after each surgical procedure. A 30-second EEG recording before skin incision and another after sternotomy were used to evaluate the effects of anesthetic technique on the EEG. The recording of the EEG was again initiated from immediately before aortic cannulation until either the second venous cannula was inserted under partial CPB or up to initial cooling. The criterion of EEG slowing at the time of cannulation was the presence of delta waves (1 to 3.5 Hz) on the child’s EEG, or a 50% or greater increase in the low-frequency activity that was not associated with changes in anesthetic depth. It was assumed that the duration of EEG slowing indicated the severity of the EEG changes. Cannulation-related EEG slowing persisting for more than 30 seconds was defined as a major alteration and shorter periods (< 30 seconds) as mild changes.

Cannulation
Stockert (Sorin, Toronto, ON, Canada) or DLP (Medtronic, Mississauga, ON, Canada) cannulae were used for aortic or venous cannulation. The diameter (mm) of the cannula indicated its size. The sequence of cannulations was as follows: aorta was cannulated first, followed by cannulation of the right atrium or superior vena cava (SVC). The inferior vena cava (IVC) was cannulated under partial CPB. If the right atrial cannula was temporarily used to support CPB, both the SVC and IVC were cannulated under partial CPB. Right atrial cannulation was used when the patient was unstable, instability was anticipated, or when only limited access was required.

CPB management
Extracorporeal circulation was achieved using a nonpulsatile pump flow (Sorin) with a membrane oxygenator (Sorin). The pump priming solution (34 to 35°C) was composed of an electrolyte solution (Ringers lactate), albumin (25% or 5%), heparin (1,000 to 5,000 units), manitol (0.5 g/kg), and sodium bicarbonate (15 to 25 mEq/L). Packed red blood cells or autologous blood and fresh-frozen plasma was added for most infants under 10 kg. The target hematocrit level during CPB was between 20% and 25%.

Anesthetic management
Premedication, when indicated, consisted of oral midazolam (0.5 mg/kg). Anesthesia was induced intravenously with sufentanil (0.5 µg/kg) and propofol (0.5 to 1.5 mg/kg). Maintenance anesthesia consisted of isoflurane (0.2 to 0.8%) and sufentanil (0.2 µg/kg/h). Isoflurane was replaced by propofol (5 to 10 mg/kg/h) in a continuous infusion during CPB. Muscle relaxants were used as required. End-tidal CO₂ (ETCO₂), central venous pressure (CVP), pulse oximetry, inspired oxygen fraction (FIO₂), rectal body temperature, and mean arterial pressure (MAP) were all monitored. Arterial blood gases and hematocrit before cannulations and during CPB were documented.

Hemodynamic control
If, during initial heart manipulation, the MAP decreased below 35 mm Hg, pharmacologic intervention was initiated by volume replacement with crystalloid (5 mL/kg) and/or administration of alpha agonists (phenylephrine boluses: 1 to 2 µg/kg), whichever was the most appropriate.

Clinical evolution
Patients were followed after surgery for neurologic complications. If clinically suspected, this was also documented by cranial ultrasound, EEG, or computerized tomography. The neurologic status, length of stay after surgery, and cardiac complications were considered as indicators of morbidity. A detailed preoperative neurologic examination was not performed.

Study groups
Cannulation procedures were identified by three parameters: type of cannulation (eg, aortic, venous), use of pharmacologic intervention, and insertion of the cannula under partial CPB. Based on the cannulation sequence before CPB, patients were divided in two groups: the SVC group, which required cannulation of the aorta and SVC, and the RA group, where the aorta was cannulated first, followed by the cannulation into the right atrium. Each group was subdivided by the use of pharmacologic intervention into: subgroup I (no intervention) and subgroup II.

Data analysis
In order to decrease intersubject variability, CBFV was expressed as a percentage relative to the precannulation baseline. Comparisons across time (repeated measures) of normally distributed physiologic variables or their intergroup differences were assessed by analysis of variance, followed by the Bonferroni/Dunn test. Simple differences between two measurements were evaluated by Student’s t test, and frequency data by Fisher’s Exact test. Multiple regression analysis (stepwise) assessed the association between CBFV and several variables as follows: MAP, CVP, size of the cannula, age, weight, ETCO₂, pulse oximetry, FIO₂, hematocrit, and expired concentration of the volatile agents. The coefficient of determination was adjusted by the number of variables. Results were regarded as significant at p less than 0.05 (two-sided). For nonnormal distributions, intergroup differences were compared with the Kruskal-Wallis statistic,followed by the Wilcoxon rank sum test adjusted for multiple comparisons (p < 0.01). Data are presented as the mean ± 95% confidence interval (CI).

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
We studied 367 cannulations in 124 children (aged 3 days to 206 months). Systemic cannulation through the aorta was followed by cannulation into the SVC (64 patients) or right atrium (60 patients). During partial CPB, cannulation of the IVC was achieved in 97 cases and into the SVC in 21. Table 1 shows the type of operations and outcomes for all patients. Pharmacologic intervention due to systemic hypotension (91%) or rapid desaturation (9%) was indicated in 44% of our patients. The control of the hemodynamic instability required administration of phenylephrine (38%), volume replacement (31%), or the combination of these two methods (31%). Patients with intervention were younger (23 ± 11 months) than those without intervention (71 ± 15 months) (p < 0.01). Children who required cannulation of the right atrium more frequently required hemodynamic support (58%) before CPB as compared with those who underwent cannulation of the SVC (31%) (p < 0.01).

Cannulations before CPB
As expected, younger children (< 24 months) usually had lower MAP (47 ± 7 mm Hg) before cannulations when compared with older children (56 ± 6 mm Hg; p < 0.01), particularly in those where pharmacologic intervention was required (p < 0.001). Aortic cannulation decreased the mean, peak, and diastolic CBFV by 10 ± 3%, 4 ± 3%, and 14 ± 8%, respectively, from their baseline (p < 0.01). Figure 1 illustrates the cannulation-related changes on the mean CBFV as a function of the MAP. The MAP, which at baseline was 53 ± 2 mm Hg, decreased by 8 ± 3% with cannulation of the aorta (p < 0.05). Subsequently, mean CBFV (95 ± 3%) and MAP (94 ± 3%) usually returned to near-baseline values 40 seconds after the cannulation (p > 0.05). With venous cannulation, MAP decreased by 12 ± 4%, and the mean, peak, and diastolic CBFV diminished by 13 ± 4%, 6 ± 3%, and 9 ± 10%, respectively, from their baseline (p < 0.01). These changes usually recovered when cannulation was successfully completed (p > 0.05). The CVP, systemic saturations, heart rate, temperature, ETCO₂, concentration of volatile agents, and FIO₂ did not change significantly (p > 0.05). In 75% of aortic cannulations, brief-Doppler elements defined as high-intensity transient signals (HITS) were identified. The HITS "count" was 8 ± 6.

View larger version (28K): [in this window] [in a new window]   Fig 1. Cerebral blood flow velocity (CBFV) and mean arterial pressure (MAP) during aortic (A) and venous (B) cannulation before institution of cardiopulmonary bypass. A second-degree polynomial regression better fitted this relationship. Arterial: CBFV (%) = 2.3 ± 2.9 (MAP) - 0.02 (MAP)2. Venous: CBFV = 6.7 + 3 (MAP) - 0.03*(MAP)2 (R2 = 0.45; 0.24). Filled circles indicate the cases that required mobilization of the aortic cannula.

Based on the stepwise regression model, the changes in mean CBFV during aortic cannulation were associated (R² = 0.40) with reductions in MAP (p < 0.0001) and the small size of the cannula (p = 0.004). During cannulation of the SVC or right atrium, mean CBFV became dependent (R² = 0.25) of the changes in CVP (p = 0.001) and MAP (p = 0.007). The diastolic CBFV suddenly disappeared (0 cm/s) during cannulation of the SVC in 7 patients and in right atrium cannulation in 2 patients, and this was followed by a reduction in mean CBFV (average 42%). In these patients, CVP in the right-internal jugular vein increased from an average of 5 (range 3 to 12) to 27 mm Hg (range 15 to 45), except for one case, where CVP did not change despite Doppler alterations. These changes were followed by transient EEG slowing in 5 patients. The reposition of the cannula returned mean and diastolic CBFV, EEG, and CVP to precannulation values. These patients were discharged from hospital without complications, except 1 who died at the end of the operation.

Study groups
Table 3 summarizes hemodynamic variables for these groups. The cannulation-related reduction in CBFV was greater in younger children with cannulation of right atrium, particularly if pharmacologic intervention was necessary (p < 0.05). This may be related to lower MAP and systemic oxygen saturations before and during cannulation as compared with the other groups (p < 0.05). Twenty-nine percent of younger children with right atrium cannulation and intervention had MAP under 35 mm Hg both before and after cannulations. This was in contrast to 20% of children who had adequate MAP, ie, greater than 35 mm Hg before cannulations, who became hypotensive (MAP less than 35 mm Hg) during these maneuvers. In general, patients requiring intervention tended to have lower CBFV and MAP as compared with those without intervention, but the changes in CVP, ETCO₂, temperature, and FIO₂ were similar. The proportion of altered EEG was similar between the two cannulation sequences (p = 0.33), but the RA-II group (cannulation of right atrium and intervention) had a slightly higher rate (p = 0.04) of EEG slowing as compared with the RA-I (cannulation of right atrium without intervention). Additionally, patients in the RA-II group required a higher dose of phenylephrine (6.6 ± 3 µg/kg) throughout the cannulation period, as compared (p < 0.01) with those in the SVC-II group (2.9 ± 1 µg/kg). The between-group differences on volume replacement were trivial (8 ± 2 vs 9 ± 6 mL/kg; p > 0.05).

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Based on the present findings, aortic and venous cannulations for institution of CPB in children usually result in transient reductions in CBFV and MAP. These alterations are compensated within the next 40 seconds after each cannulation, except for some cases where cannula malposition leads to a compromised cerebral perfusion as suggested by low CBFV and EEG slowing. These cerebral alterations are associated with a transient decrease in cardiac output due to impairment of venous return or a partial obstruction by the aortic cannula [1–3].

The absence of diastolic Doppler flow that resulted in low CBFV during venous cannulation was associated with increases in the pressure of the internal jugular vein as a consequence of SVC obstruction by the cannula [2]. If this situation persists, the EEG deteriorates, suggesting neuronal dysfunction [2, 6]. Although SVC obstruction may be suspected by high internal jugular venous pressures, cerebral function indicators can reflect these alterations even in cases when jugular catheters are nonfunctional [7].

In our study, undesirable cerebral effects associated with cannulation were more common in young infants with cannulation of the right atrium. These findings may be more related to the hemodynamic status of our patients rather than the type of cannulation, as the right atrium was typically chosen because the patient was hemodynamically unstable or instability was anticipated. Although pharmacologic intervention before cannulation attenuated the affects of cannulation in older children, younger infants of the group RA-II showed higher rates of EEG slowing despite the use of intervention. Although these alterations were related to a reduced cardiac output as a consequence of the hemodynamic instability, previous reports [8–10] suggest that some young infants may have a limited range of cerebral autoregulation, which may not allow to compensate for such critical reductions of arterial blood pressure. In consequence, higher systemic blood pressures may be helpful for these patients when the risk of hemodynamic alterations is present.

Brain ischemia during normothermia is manifested by EEG slowing [3, 6]. While the possibility for ischemic disorders in the infant brain depend on the duration of critical reductions in arterial blood pressure [8–12], the tolerance by the human brain to these effects is unknown. Longer periods of ischemia appear to be necessary to produce permanent brain injury, but even short intervals could generate minor or subclinical deficits [11]. Our study indicates that some of our infants had transient periods of low CBFV accompanied by electrocortical alterations associated with cannulations. Although two of these patients had postoperative cerebral complications, we were unable to determine if those transient changes adversely affected neurologic outcome, as subsequent factors such as CPB, the use of total circulatory arrest, and type of repair were involved in the final outcome. A larger, homogenous patient population with more specific neurologic evaluation would be necessary to answer this question.

Institution of CPB induced a transient EEG slowing in one-half of our patients, particularly infants, but no major alterations were detected when venous cannulation was achieved under CPB. While infants were more likely to receive blood or packed red blood cells as a component of the priming solution, our study did not find any association between the type of priming and the rate of transient EEG changes during initiation of CPB. Although cerebral blood flow has been documented to increase with reduction in hematocrit [13], changes in cerebral oxygen delivery and brain oxygen extraction that occur during hemodilution as a result of institution of CPB may be associated with this cerebrocortical response [14].

TCD measures the velocity of red blood cells rather than blood flow [3, 4]. Several reports support the notion that changes in CBFV correlate with alterations in regional cerebral blood flow [15–17], a relationship that appears to be imprecise under conditions of hypothermic CPB [18]. In addition, TCD has been shown to be sensitive to the presence of small particles or air in the vascular lumen [19], but cannot determine size and composition. This investigation confirms that aortic cannulation is a source of these Doppler signals in children [19], and that IVC cannulation during partial CPB may introduce air and/or particles into the systemic circulation in the presence of interseptal communications. The negative pressure in the IVC cannula plus a Venturi effect may pull air through loose purse-strings into the lumen of the vessel. Subsequently, microbubbles or particles may reach the systemic circulation if a large right-to-left shunt is present. In our study, this potential phenomenon did not occur during cannulation of SVC or right atrium, as these structures were cannulated before CPB.

In summary, TCD and EEG demonstrate the effects of aorto-venous cannulations on the functional status of the cerebral vasculature in children. The measures designed to reduce the effects of compromised venous return (eg, vasopressors, volume) will minimize these effects in older children, but in small infants, larger cerebral hemodynamic changes are expected. In some instances, venous cannulation impairs cerebral venous drainage, which may be followed by Doppler flow and EEG alterations. The use of these indicators during pediatric cardiac operations enhances the appreciation of the effects of our manipulations on brain circulation.

	Acknowledgments

 
Doctor Rosendo A. Rodriguez was recipient of the Popham Fellowship Award. The authors appreciate the cooperation of all the staff in the cardiac operating room. The clerical work by Carlos and David Rodriguez is gratefully appreciated.

	References

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