Intraoperative NA administration prevents fluid overload and counteract intraoperative hypotension[1]. This study revealed that intraoperative NA administration in elderly patients undergoing major oncologic surgery significantly reduced intraoperative fluid replacement, bleeding, transfusion, and postoperative urinary tract infections, but had no impact on other in-hospital complications.
Clinical studies have confirmed that intraoperative NA administration can promote platelet aggregation and clot firmness in patients undergoing coronary artery bypass grafting[15]. Adrenergic α1 receptor exists on the surface of platelets, and NA can promote platelet aggregation by activating α1 receptor and ADP pathway[16]. Theoretically, NA activates α1 receptor, contracts arterioles, and impairs mesenteric microcirculation, but activation of β1 receptor improves cardiac function and promotes mesenteric microcirculation[17]. That may be the mechanism which made the results of animal studies inconsistent[5, 18] and a great heterogeneity among subjects in clinical studies[19–21], and it is very difficult to confirm the relationship between NA administration and outcomes.
It was reported that intraoperative NA administration at a rate of 0.05 or 0.075 µg/kg/min could maintain blood pressure more stably than 0.025 µg/kg/min after spinal block in cesarean section[22]. In this study, the intraoperative NA infusion rate was 0.04-1.0 µg/kg/min, which could maintain the stability of blood pressure and reduce fluid replacement, but increased intraoperative lactate production. One study reported that intraoperative restrictive fluid therapy combined with NA administration decreased postoperative complications and hospital stay in radical cystectomy[23], and another study found that combination of intraoperative restrictive fluid therapy and NA infusion increased the risk of AKI after radical cystectomy, and NA was not a risk factor[24]. The results of this cohort study showed that intraoperative NA infusion reduced postoperative urinary tract infection, and did not affect cardiac, pulmonary, and other in-hospital complications. So, NA infusion at a rate of 0.04–0.1µg/kg/min is relatively safe during major oncologic surgery in elderly patients.
As NA is a strong adrenergic α1 agonist and has a very high property of constricting arteries and veins, the major concern of peripheral administration is extravasation which might cause severe and long-lasting skin damage[25]. One recent retrospective cohort study found that peripherally administered NA did not result in more adverse events including skin necrosis[26]. In our study, NA was administered mostly via a central venous line, we might be cautious to use peripheral route for NA infusion.
This study has some limitations, the advanced monitoring methods such as CO and PPV were not commonly used in our clinical practice; and this study is a retrospective cohort study, the results should be verified in the near future by a RCT with large samples.
In summary, this retrospective cohort study showed that intraoperative noradrenaline administration reduced fluid replacement, blood loss, and transfusion in elderly patients undergoing major oncologic surgery, although it increased the difference of lactate level between the end of surgery and baseline, it reduced postoperative urinary tract infection, and had little impact on other postoperative in-hospital complications and mortality. Thus, it is recommended that noradrenaline can be safely administered intraoperatiely in elderly patients undergoing major oncologic surgeries.