Aortic arch reconstruction: deep and moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion

Abstract

Objective:

To compare the effects of moderate and deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (SACP) during aortic arch surgery in adult patients and to offer the evidence for the detection of the temperature which provides best brain protection in the subjects who accept aortic arch reconstruction surgery.

Methods:

A total of 109 patients undergoing surgery of the aortic arch were divided into the moderate hypothermic circulatory arrest group (Group I) and the deep hypothermic circulatory arrest group (Group II). We recorded the data of the patients and their cardiopulmonary bypass (CPB) time, aortic clamping time, SACP time and postoperative anesthetized recovery time, tracheal intubation time, time in the intensive care unit (ICU) and postoperative neurologic dysfunction.

Results:

Patient characteristics were similar in the two groups. There were four patients who died in Group II and 1 patient in Group I. There were no significant differences in aortic clamping time of each group (111.4±58.4 vs. 115.9±16.2) min; SACP time (27.4±5.9 vs. 23.5±6.1) min of the moderate hypothermic circulatory arrest group and the deep hypothermic circulatory arrest group; there were significant differences in cardiopulmonary bypass time (207.4±20.9 vs. 263.8±22.6) min, postoperative anesthetized recovery time (19.0±11.1 vs. 36.8±25.3) hours, extubation time (46.4±15.1 vs. 64.4±6.0) hours; length of stay in the intensive care unit (ICU) (4.7±1.7 vs. 8±2.3) days and postoperative neurologic dysfunction in the two groups.

Conclusion:

Compared to deep hypothermic circulatory arrest, moderate hypothermic circulatory arrest can provide better brain protection and achieve good clinical results.

Keywords

deep hypothermic circulatory arrest moderate hypothermic circulatory arrest brain protection aortic arch surgery CPB

Despite the progress made in the past decades with the operative management of aortic diseases involving the transverse aortic arch, replacement of this portion of the vessel remains a surgical challenge and is associated with significant morbidity and mortality due to ischemic end-organ damage occurring during the circulatory arrest period. The primary strategy for cerebral protection could be the key points for successful surgery. The main method for cerebral protection has traditionally been (DHCA+SCAP) to reduce metabolic demands and oxygen consumption and, thus, increased tolerance to hypoxia.^1–3 The optimal temperature for DHCA+SCAP during arch surgery in adults remains unclear.

The first successful series of arch reconstructions using DHCA with body temperatures of 18°C was applied in 1975.⁴ Deep hypothermia significantly reduces cerebral oxygen requirements; however, the safe duration of DHCA is limited and prolonged periods of DHCA are associated with end-organ ischemia and postoperative neurologic dysfunction.^5–6 The scholars from Emory University Hospital instituted a protocol of hypothermic circulatory arrest and unilateral SACP (uSACP) through the right axillary artery for all cases requiring aortic arch reconstruction in 2004. Initially, they suggested deep hypothermia (18° to 22°C) and achieved acceptable outcomes. However, in order to limit cardiopulmonary bypass times and ameliorate the adverse effects of profound hypothermia, they gradually began to use more moderate levels of hypothermia.⁷ This study was conducted to evaluate the efficiency of deep and moderate hypothermia for brain protection in aortic arch surgery with antegrade cerebral perfusion.

Patients and Methods

Between January 2013 and December 2014, a total of 109 patients underwent aortic arch surgery at our institution, using right axillary artery cannulation, hypothermic circulatory arrest and uSACP in this study. Patients excluded from this analysis included those with other anatomic sites for arterial cannulation, hypothermic circulatory arrest without uSACP, aortic root or ascending aortic replacement without arch reconstruction and descending aortic surgery. All patients underwent surgical correction of aortic arch abnormalities under cardiopulmonary bypass and deep DHCA+uSACP (Group I, 59 patients) or DHCA+uSACP with moderate hypothermia (Group II, 50 patients). The method for brain protection was selected by the surgeon. Detailed preoperative patient characteristics are presented in Table 1. This study was approved by the Institutional Review Board at NanJing Medical University in compliance with Health Insurance Portability and Accountability Act regulations and the Declaration of Helsinki. The Institutional Review Board waived the need for individual patient consent.

Table 1.

Characteristics of the cohort.

	Group I (n=50)	Group II (n=59)	P
Male/female	28/22	33/26	0.32
Age (years)	54 ± 9.5	50.2 ± 7.5	0.1
Body weight (kg)	68.2 ± 5.3	69.4 ± 4.9	0.25
Hypertension	10	14	0.43
DM	8	10	0.35
High cholesterol	11	14	0.18
Preoperative diagnosis
Acute aortic dissection	46	57	0.22
Chronic aortic dissection	4	4	0.48
Redo	1	2	0.5
COPD	4	5	0.7
Renal failure	0	0	–

DM: diabetes mellitus; COPD: chronic obstructive pulmonary disease.

Surgical technique

Anesthetic technique and monitoring was the same as that used for other cardiac surgical procedures, except for the placement of bilateral radial arterial lines. Invasive monitoring included the use of a pulmonary artery catheter and a left radial-femoral arterial line to allow measurement of systemic perfusion pressures during cardiopulmonary bypass. A Foley catheter with a temperature probe was inserted to measure bladder temperature. This was used as our indicator of core body temperature. Electroencephalogram monitoring was routinely performed in all cases. Intraoperative transesophageal echocardiography was used in all patients. The HL-20 (Maquet, Hirrlingen, Germany) was used for CPB. The extracorporeal circuit was primed using 200–220 ml of a solution that included donor red blood cells (to maintain an hematocrit of at least 30%), 20% albumin, sodium bicarbonate, mannitol and heparin. We used the right axillary artery for cannulation.

CPB was performed with a flow of 2.0-2.8 L.kg.min with about 40 min of prior cooling to a nasopharyngeal temperature of 18–25°C, with a temperature gradient not exceeding 10°C. The blood gases were maintained in an alpha-stat strategy, with a target pCO₂ of 40 mmHg. The goal core body temperature was variable and depended upon several factors, including age, preoperative renal function, aortic pathology and the complexity of the planned aortic arch reconstruction.

DHCA was carried out when the nasopharyngeal temperature reached the goal temperature. SACP, with a flow of 5-8 mL·kg·min, was performed through the right axillary artery. The left common carotid artery, the left subclavian artery and the descending aorta were clamped after the start of uSACP. Depending on the individual anatomy, aortic arch reconstruction used procedures such as ascending aorta replacement, right arch replacement and Bentall and Sun’s procedure (total arch replacement using 4-branched graft with implantation of a special stented graft in the descending aorta).⁸ The list and frequency of concomitant procedures is summarized in Table 2.

Table 2.

Surgical procedures.

Dada	no
Ascending aorta replacement + Sun’s procedure	63
Ascending aorta replacement + right arch replacement	25
Bentall + Sun’s procedure	9
Bentall + right arch replacement	7
Ascending aorta replacement + Bentall + right arch replacement	5

Statistical analysis

Patient demographic, preoperative, intraoperative, early morbidity and mortality data were collected and recorded prospectively. Statistical analysis was performed using SPSS for Windows software (version 13.0, Chicago, IL, USA).Continuous variables were expressed as mean±standard deviation, and categorical variables were expressed as number (percentages).The incidence of perioperative major neurologic injury and post-op 30-day mortality (including perioperative death) were compared using Chi Squared or Fisher’s exact test; a two-tailed p-value of less than 0.05 was considered statistically significant. In this study, major neurologic injury defined the patients who appeared one of delayed recovery, epilepsy, cerebral embolism, coma, paralysis, paraplegia, anxiety, irritability and delirium.

Results

Preoperative demographics of subjects

One hundred and nine patients comprised the statistical analysis population. Group I had 50 patients with 28 males vs 59 patients with 33 males in Group II. The median age was similar in both groups: 54±9.5years in Group I and 50.2±7.5 years in Group II. Medical histories included hypertension (10 vs 14), diabetes mellitus (DM) (8 vs 10), preoperative diagnosis, chronic obstructive pulmonary disease (COPD), redo-surgery, renal failure and high cholesterol (11 vs 14). There was no difference in the above characteristics of the patients in the two groups (Table1).

Extracorporeal circulation data

The median CPB time was considerably longer in Group I than in Group II (263.4±20.9 vs 207±20.9 minutes), whereas the aortic cross-clamping time (111.4±58.4 vs 115.9±16.2 minutes) and the selective cerebral perfusion time (27.4±5.9 vs 23.5±6.1 minutes) did not differ significantly between the two groups (Table 3).

Table 3.

Operative data.

	Group I	Group II	P
Aortic cross-clamp time (min)	111.4 ± 58.4	115.9 ± 16.2	0.80
SACP (min)	27.4 ± 5.9	23.5 ± 6.1	0.29
CPB (min)	263.4 ± 20.9	207 ± 20.9	<0.01

SACP: selective antegrade cerebral perfusion; CPB: cardiopulmonary bypass.

Mortality (30-day)

The overall 30-day mortality was 4.6%. There was no statistically significant difference between the groups in terms of 30-day mortality. Four patients in Group II died: one patient from multi-organ failure, two patients from cardiac arrest and the last patient from low cardiac output syndrome. One patient in Group I who underwent emergency surgery for an acute dissection died (cardiogenic shock).

Postoperative events

There were significant differences in the postoperative anesthetized recovery time (36.8±25.3 vs. 19.0±11.1) hours, intubation time (64.4±6.04 vs. 6.4±15.1) hours, length of stay in the ICU (8±2.3 vs. 4.7±1.7) days and postoperative neurologic dysfunction of the two groups. Moreover, there were 14 (28%) neurological events in Group I and 10 (16%) in Group II. Seven Group I patients and two Group II patients had temporary neurological dysfunction/transient clinical seizures, which fully recovered within a month. One patient from the DHCA+SCAP group had prolonged awakening and right-sided hemiparesis after surgery and continues rehabilitation for hemiparesis. The results of univariate and multivariate analyses for those postoperative events are presented in Table 4.

Table 4.

Postoperative events.

	Group I	Group II	P
Postoperative awake time (min)	36.8 ± 25.2	19.0 ± 11.1	<0.01
Extubation time (min)	64.4 ± 6.0	46.4 ± 15.1	0.039
Length of ICU stay (day)	8 ± 2.3	4.7 ± 1.7	<0.001
Neurologic injury	14/50 (28%)	10/59 (16%)	<0.01
TND	12	10	–
PND	2	0	–
Renal failure	1	0	–
Mediastinal hemorrhage	0	1	–
visceral ischemia	1	0	–

TND: temporary neurologic deficits; PND: permanent neurologic deficits.

Discussion

Griepp et al. first described the use of hypothermic circulatory arrest in aortic arch surgery in 1975, which was later supplemented by, first, retrograde and, then, antegrade brain perfusion. Asou et al. used selective antegrade perfusion with aortic arch pathology in 1983.⁹ Over the past two decades, deep hypothermic circulatory arrest in combination with either continuous antegrade or retrograde cerebral perfusion has evolved into a standard method of cerebral protection during aortic arch reconstruction in the majority of high-volume aortic centers. This strategy has reduced morbidity and mortality and has enabled arch replacement to be accomplished, even in the setting of complex arch pathology requiring extended periods of circulatory arrest. However, DHCA has been shown to have adverse effects upon multiple organ systems. In an attempt to avoid the morbidity associated with DHCA, to reduce CPB times and to improve neurologic outcomes, we adopted a strategy of DHCA with adjunctive uSACP as our preferred method of cerebral protection during aortic arch reconstruction; yet, controversy remains concerning the influence of perfusion temperature.

Deep hypothermia

Low temperature cannot completely inhibit cerebral metabolic rate metabolism, though it reduces it. Furthermore, prolonged circulatory arrest time will produce ischemic injury. Meanwhile, deep hypothermia can increase inflammation, which can lead to postoperative coagulopathy. Some researchers have observed that deep hypothermic cerebral metabolic inhibition did not bring the expected benefits; meanwhile, moderate hypothermic SCP maintains energy metabolism by reducing the level of inhibition of brain metabolism. Moreover, moderate hypothermia also can prevent the hemoglobin oxygen dissociation curve moving to the left which will increase the release of oxygen to the tissue. In a word, mild hypothermia is more favorable than deep hypothermia on cerebral protection.¹⁰

Moderate hypothermia

There are research data which show that the body’s metabolic rate at a body temperature of 28^oC is only 60% of the metabolic rate at normal temperature and only about 40% at 25°C. In addition, the gap of metabolic rate between the patients under anesthesia and awake is15%. Therefore, using moderate hypothermia cardiopulmonary bypass, which can cooled down to 25-28°C, produces 35%-50% of the body’s normal metabolic rate.¹¹ There is also information which shows that the autoregulation function of cerebral vasculature is normal when subjects are in moderate temperature anesthesia during cardiopulmonary bypass. Compared with 18°C, the cerebral blood flow, cerebral metabolic rate of oxygen and cerebral perfusion pressure were significantly higher at 25°C during SCP. Besides that, utilizing moderate hypothermia temperature can significantly shorten the duration of CPB, which can prevent and reduce cardiopulmonary bypass-related complications. At the same time, systemic moderate hypothermia can shorten the cooling and rewarming time, greatly reducing CPB time, which cuts down the incidence of complications caused by prolonged cardiopulmonary bypass. Notably, results of our data statistically also confirmed moderate hypothermia DHCA+SCP in protecting brain surgery complex aortic arch is better than the depth of hypothermia.

pH management

In addition, methods of CPB blood management and the rewarming process are also part of the process of cerebral protection and cannot be ignored. The impact of blood management practices on brain function is debatable. At present, the main management methods comprise pH-stat, alpha-stat and pH-α stat. α steady-state can be relatively stable enzymes and functional protein activity at low temperatures, thereby, maintaining a relatively stable metabolism and helping to maintain homeostasis while pH-stat has the advantages of balancing the cerebral oxygen supply and demand. However, alpha-stat can provide intracellular acid-base status in moderate hypothermia during the CPB.¹² Therefore, we used alpha-stat for DHCA+SCP.

Temperature management of the rewarming process

Done incorrectly, the rewarming process can easily cause cerebral complications and it is very necessary to control it. We usually use cold reperfusion 10-20 minutes before rewarming, until the jugular bulb oxygen saturation (SjO₂) >80% and, after left common carotid anastomosis, the rewarming process is started when the water temperature is 26°C (keep the water temperature - nasopharyngeal temperature difference <3°C, nose - bladder temperature difference <6°C) then, keeping the water temperature when the nose temperature has reached 35°C, balancing nose - bladder temperature <3°C and increasing the water temperature to 38°C. Finally, we stop the CPB when the bladder temperature reaches 36.5°C. At the same time, the room temperature is raised to 24-26°C and the blanket water temperature is set to 39°C, after cutting down the pump.

Comment

Currently, more and more surgeons have been using the moderate or higher hypothermic circulatory united antegrade cerebral perfusion technique in aortic arch surgery cerebral protection because the temperature can reduce the time to improve cooling and rewarming time and the deep hypothermia associated inflammation and ischemia-reperfusion injury, but the relatively high temperature will increase the metabolic rate of the organ and may cause unpredictable postoperative complications of internal organs and the spinal cord. Above all, it is reasonable for surgeons to make the decision of temperature management in aortic arch surgery circulatory arrest procedures according to the patient’s condition, in the case of preoperative nervous system and the circulatory arrest time.

Limitations

This report has several limitations. First, the retrospective, non-randomized nature of the study requires caution when interpreting the results. Some important information is unavailable, such as baseline renal function, gestational age, etc., often due to the urgent nature of the surgery and imperfect methods of record collection and storage during the initial period of the study. Second, the relatively small sample size may have limited statistical power for the analyses. Additionally, the diagnosis of neurological events in this category of patients is often subjective, which may have introduced a detection bias into the study. A prospective, randomized study is planned that will determine the effect of temperature on renal dysfunction in aortic arch surgery; furthermore, molecular laboratory markers may be the best supplement for the study.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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