Temporary restriction of right ventricle–pulmonary artery conduit flow using haemostatic clips following Norwood I reconstruction: potential for improved outcomes

Abstract

Improved outcomes of the Norwood procedure in hypoplastic left heart syndrome have been achieved by the manipulation of the pulmonary:systemic flow ratio (Qp:Qs) in the early post-operative period, with focus on improving systemic perfusion. As an extension of this Qp:Qs-limiting strategy, we evolved a novel surgical technique to achieve transient flow restriction in the right ventricle–pulmonary artery (RV–PA) conduit for the first 48 h, using haemostatic clips, in a cohort of patients and compared the early outcomes with a non-clipped cohort. Clips were subsequently removed at 48 h at the time of definitive chest closure. We performed RV–PA shunt flow clipping in 37 patients; 75 historical controls had not received clips. Groups were matched for weight, size of ascending aorta, anatomy and circulatory arrest times. Thirty-day mortality was lower in the clipped cohort (2 of 37; 5.4%) versus the unclipped cohort (10 of 75; 13.3%). The minimum blood lactate levels within the first 24 h post-surgery in the unclipped group were significantly higher (P = 0.049), with a significantly lower Qp:Qs in the first 6 h in the clipped patients. These data suggest that limiting Qp:Qs in the early post-operative period following the Norwood procedure may help in the post-operative management of these difficult patients. These results warrant further study.

INTRODUCTION

Improved early outcomes of the Norwood procedure in hypoplastic left heart syndrome have been achieved through the use of the right ventricle–pulmonary artery (RV–PA) Sano conduit and by manipulating the pulmonary:systemic blood flow ratio (Qp:Qs) in the early post-operative period in favour of Qs [1–3]. Following two early preliminary reports of flow limitation in modified Blalock–Taussig shunts in the Norwood procedure as a means of limiting Qp and enhancing Qs [4, 5], we adopted a policy in our institution of clipping all RV–PA conduits at the time of the Norwood I procedure and continued following 100% 30-day survival for the first 10 patients. We report here the details of this technique as well as the early outcomes with the first cohort of such patients.

PATIENTS AND METHODS AND RESULTS

We identified 37 patients from February 2009 to September 2010 who had undergone Norwood procedures with a Sano conduit that had been reversibly clipped. The comparison group comprised 75 historical control patients with unclipped conduits in the 2 years immediately preceding the study period. Patients were comparable in for pre- and intra-operative risk factors (Table 1). The Sano-Norwood procedure was performed, employing deep hypothermic circulatory arrest with systemic cooling to 18°C and selective antegrade cerebral perfusion [1]. The RV–PA connection was constructed using a GORE-TEX^® graft (WL Gore and Associates UK Ltd, Livingstone, Scotland): 5.0 mm for patients ≥2.5 kg and 4.0 mm for patients <2.5 kg. Target arterial oxygen saturations (SaO₂) were 70–80% with mixed venous oxygen saturations (SvO₂) of 40–­50% on fractional inspired oxygen of 0.5. Target mean arterial blood pressure was 50–55 mmHg; arterial blood gas analysis was performed to ensure a target lactate level of <5.0 mmol/l. To achieve these goals, the RV–PA conduit was clipped using a medium-sized Ligaclip (Ethicon Inc., Somerville, NJ, USA; Fig. 1A and B). Clips were applied in the operating room at the conclusion of the surgical reconstruction, after separation from cardiopulmonary bypass (CPB). Haemostatic clips were subsequently removed at 48 h at time of delayed sternal closure. Qp:Qs was calculated according to the Fick method using values for SaO₂ and SvO_2, as described for patients following the Norwood procedure [5]. All patients received post-operative intravenous heparin and were subsequently converted to enteric aspirin. The ventilatory strategy and pharmacological management of systemic vascular resistance and cardiac contractility in both groups was the same. We determined minimum 24-h blood lactate levels as a surrogate for Qs and predictor of 30-day survival, as well as mean Qp:Qs for each 6-h time interval epoch post-Norwood.

Table 1:

Patient characteristics and intra-operative data

	Patient cohort
	Unclipped	Clipped
Basic patient variables
Number of patients (n)	75	37
Weight (kg)a	3.1 (2.1–5.3)	3.1 (2.2–4.2)
Height (cm)a	50 (43–71)	50 (44–55)
Ascending aorta size (mm)a	3.0 (1.0–7.0)	2.5 (1.5–5.0)
Morphologic type
AAMA [n (%)]	26 (34.7)	6 (20.0)
ASMS [n (%)]	30 (40.0)	14 (46.6%)
AAMS [n (%)]	12 (16.0)	5 (16.7)
Other [n (%)]	7 (9.3%)	5 (16.7)
Not specified (n)	0	7
Intra-operative variables
Cardiopulmonary bypass time (CPB time; min)a	114 (86–279)	117 (81–213)
Cross-clamp time (CCT; min)a	50 (22–121)	49 (25–89)
Other features
Impaired RV function preoperative [n (%)]	14/75 (18.7)	4/29 (13.8)
Antenatal diagnosis [n (%)]	55/75 (73.3)	27/37 (73.0)

^aContinuous variables reported as medians and the corresponding range.

Figure 1:

Intra-operative photographs of RV–PA conduit showing insertion of the unclipped (A) or clipped (B, arrowheads) conduit (*) to the right pulmonary artery. Also shown at the top of the images is the innominate artery shunt for CPB arterial return. (C) Minimum 24-h arterial blood lactate levels in unclipped versus clipped patients. The box and whisker plots show the median values for blood lactate (bold horizontal line within boxes) as well as the 95% range (whiskers). Outliers are indicated by circles. Many more outliers with higher lactate values are seen in the unclipped cohort of patients; this was statistically significant (the Kruskal–Wallis rank-sum test). (D) Values for the Qp:Qs ratio for unclipped (group 1; blue) and clipped (group 2; green) patients. The mean ± SEM for each 6-h time interval epoch post-Norwood I is shown. The Qp:Qs ratio was significantly lower (P < 0.05; Kruskal–Wallis) for clipped patients during epoch 1 (first 6 h) and epoch 10 (55–60 h). Epoch 10 is after clip removal (red arrow). By epoch 11, values for Qp:Qs in the clipped cohort increase again.

Thirty-day mortality was lower in the clipped (2 of 37; 5.4%) versus the unclipped group (10 of 75; 13.3%), although this was not statistically significant (Fisher's exact test; P = 0.331). Further, the 90-day mortality was also lower in the clipped cohort (3 of 37, 8.1% vs. 11 of 75, 14.7%, P = 0.381). The minimum arterial blood lactate values within the first 24 h following surgery in the two groups were significantly higher in the unclipped cohort, therefore reflecting a likely lower Qs in this group (Fig. 1C). Examining the Qp:Qs ratio for the clipped versus the clipped patients revealed a significantly lower mean Qp:Qs in the clipped cohort during the first 6 h post-Norwood (epoch1) as well as early after clip removal (epoch 10; Fig. 1D). By epoch 11 (61–66 h post-Norwood), however, Qp:Qs for the two cohorts was similar.

DISCUSSION

Recent work has suggested that optimizing the Qp:Qs ratio in favour of Qs during the early post-Norwood period may have beneficial effects in terms of blood lactate levels and patient survival, with higher minimum 24-h lactate being significantly associated with higher mortality [1]. In this study, we aimed to achieve this by temporarily clipping the RV–PA shunt. Minimum 24-h lactate levels were significantly lower in the clipped cohort and Qp:Qs during the first 48 h post-surgery tended to be lower in the clipped patients, with a significant difference within the first 6 h. Interestingly, the Qp:Qs ratio in the clipped patients remained lower than that in unclipped patients initially after clip removal and formal chest closure at 48 h, though increased thereafter. Importantly, Charpie et al. [6] have demonstrated that the largest changes in Qp:Qs following the Norwood procedure occur during the first 6 h and that patients requiring post-operative mechanical circulatory support had higher Qp:Qs values during the first 6 h. Clipping the Sano shunt therefore appeared to further limit Qp:Qs, despite the anticipated transient increase in pulmonary vascular resistance observed early after the use of CPB in neonates and infants [7].

CONCLUSION

While era effects due to the historical nature of the control, unclipped cohort cannot be eliminated, the data here suggest that transiently limiting Qp:Qs using haemostatic clips in the early post-operative period following the Sano-Norwood procedure is associated with beneficial effects on Qp:Qs in favour of Qs (indirectly reflected by lower 24-h lactate levels) and both 30- and 90-day survival in comparison with a conventional strategy using unclipped Sano conduits. We suggest that further investigation of this modification is warranted, ideally through a prospective randomized study.