The performance of major spinal surgeries increased significantly during the previous 2 decades because they provide good functional outcomes [1]. Complex spinal surgeries are associated with prolonged procedures, prone position, and blood loss, all of which can contribute to adverse postoperative events [2]. Hypotension and fluctuations in blood pressure during spinal surgery in the prone position under anesthesia are common [3]. Previous studies showed that the main cause of hypotension in the prone position during lumbar spinal surgery is an inadequate preload, leading to a decrease in the stroke volume (SV) and cardiac index [4]. Furthermore, decreased pulmonary compliance and a rigid supportive spine frame contribute to a decrease in the SV [5]. Elevated risks of end-organ injury owing to intraoperative hypotension have been reported [6]. A fall in splanchnic perfusion results in neurological injury and an intramucosal acidosis of the gut [7], leading to a cascade of events that impair the postoperative neurological outcome as well as gastrointestinal and renal functions. Careful management of fluid and blood pressure during surgery may improve patient outcomes.

The first goal-directed therapy (GDT) was employed by Shoemaker et al. [8] in 1988; they used a pulmonary artery catheter to guide oxygen delivery perioperatively. However, for subsequent GDT studies, less invasive monitoring systems have been used to measure intraoperative SV and cardiac output to guide fluid therapy [9]. The results of randomized, controlled trials and meta-analyses suggest that intraoperative GDT is associated with improved outcomes and reductions in hospital stays for patients undergoing cardiac, major abdominal, and major orthopedic surgeries [10,11]. Next, pulse-pressure variation (PPV) is based on heart-lung interactions and cyclic changes in the SV induced by mechanical ventilation in the closed-chest condition [12]. PPV monitoring has been used for predicting fluid responsiveness. This method is not as invasive as other methods and is not operator dependent; further, it has been validated for use in patients in the prone position [13].

We hypothesized that PPV monitoring coupled with a treatment algorithm could decrease the incidences of intraoperative hypotension, intraoperative blood transfusion, and perioperative complications in patients undergoing elective complex spine surgery in the prone position as compared to standard hemodynamic management.

During the 20-month study period, 170 patients were eligible. However, 110 were excluded; 42 were excluded because they were aged ≥70 years, 33 because they presented with an estimated glomerular filtration rate of <60 mL/min, 21 owing to a history of severe cardiovascular disease, 12 because they presented with a BMI of >30 kg/m², and two because they presented with a complete cord lesion. Sixty patients fulfilled the inclusion criteria (Fig. 2); thus, 30 patients were randomized into each of the two study arms. However, three patients in the GDT group were subsequently withdrawn from the study because of a protocol violation in two cases and a change to the lateral position during the operation in the third case.

No differences were found in the patients’ demographic characteristics in terms of age, sex, BMI, ASA physical status, and comorbidities. The preoperative investigations, including the complete blood counts and creatinine levels, were normal and comparable for the two groups (Table 1). Eighty percent of the patients in the control group experienced hypotension compared with 66.6% of those in the GDT group (p=0.25). Most hypotensive episodes occurred after the induction of anesthesia. Sensitivity analysis showed that 16 (53.3%) patients in the control group and 9 (33.3%) in the GDT experienced post-induction hypotension (p=0.13); further, 7 (23.3%) patients in the control group and 4 (14.8%) in the GDT group experienced post-positioning hypotension (p=0.42).

The operations consisted of (1) multilevel laminectomies, (2) laminectomies involving 1–3 levels of instrumentation, (3) laminectomies involving more than three levels of instrumentation, and (4) laminectomies with tumor removal. The four types were equally distributed between the two groups. Thirty-three patients from both the groups exhibited significant blood loss (>500 mL). The estimated blood loss and blood transfusion amount of the two groups did not differ (Table 2). The median values of the intraoperative red blood cell transfusions were zero for both the groups, and no differences were found in their intraoperative fluid administration and urine outputs.

On postoperative day 1, the hematocrit level was 32.0%±4.9% for the control group and 29.9%±4.6% for the GDT group (p=0.08). Although the postoperative complication rate and total length of stay were reduced for the GDT group, the differences were not significant (Table 3). Two patients in the control group continued with mechanical ventilation in the intensive care unit (ICU); one exhibited experienced massive blood loss (6,000 mL), while the other received a prolonged operation (>6 hours). In the subgroup analysis including more invasive surgical procedure (laminectomies involving more than three levels of instrumentation and laminectomies with tumor removal), the results remain robust, except for the postoperative bowel ileus that GDT provided promising result with marginally significant effect (p=0.058) (Supplement 1). From our exploratory analysis, the patients who experienced hypotension seemed to present with more postoperative complications and delayed recovery of bowel function as compared to those without hypotension (p=0.005) (Table 4).

The perioperative maintenance of an adequate intravascular volume status is important for the achievement of intraoperative hemodynamic stability and optimal postoperative outcomes. Both, hypovolemia and hypervolemia decrease tissue perfusion and may result in organ failure [17,18]. GDT is a method of optimizing perioperative fluid administration and reducing the incidence of postoperative organ dysfunction. With regard to spine surgery, Picard et al. [15] conducted a randomized, controlled trial using an esophageal Doppler as a hemodynamic guidance during surgery. Their study showed that the durations and episodes of hypotension were greater in the standard care group than those in the GDT group. In contrast to the findings of the Picard study, the observed effect of the application of the PPV-guided GDT used in our protocol did not significantly reduce the incidences of intraoperative hypotension, despite similar clinical characteristics to those in the Picard study. We reported only 1–2 episodes of hypotension per patient, compared with 3–7 episodes in the Picard study. There could have been several factors that contributed to the differences; for instance, we used desflurane to maintain anesthesia, while Picard et al. [15] used propofol target-controlled infusion. Several studies reported fewer episodes of intraoperative hypotension of inhalation anesthesia with desflurane or sevoflurane than that with propofol [19,20]. This study reported a blood loss of about 500 mL; however, our intraoperative transfusion rate was very low (median, 0; IQR, 0–1). We used the transfusion guideline obtained from the clinical evidences and guidelines for red blood cell transfusions [14]. These guidelines exhibit a common theme as follows: avoid unnecessary transfusions. In comparison, Bacchin et al. [16] retrospectively reviewed the outcomes in 23 patients who received spine surgery and whose fluid administration had been managed with the GDT protocol as compared to that in 23 matched controls who received a liberal fluid therapy. They found that the application of GDT based on SV variation can lead to a significant reduction in blood loss (median [IQR] from 250 [0–500] mL to 0 [0–250] mL) with a reduction of 1 unit of transfused red blood cells, better postoperative respiratory performance, a shorter ICU stay, and a faster normalization of bowel function [16]. However, in this retrospective study, no criteria were present for blood transfusions leading to over-transfusion despite limited blood loss. Few studies reported on goal-directed fluid therapy in spine surgery. Our study results did not reveal any significant benefits of the GDT protocol in comparison to that of standard treatment. Many factors might contribute to this finding. First, the patients in the present study received the same amount of fluid whether they were or were not subjected to PPV monitoring. During the previous decade, the concept of perioperative fluid therapy changed drastically, resulting in the overall intraoperative fluid administration decreasing to the minimum necessary amount [21]. This concept may have helped to lower the incidence of complications and morbidity and may have reduced the marginal benefits of the alternative GDT strategy. Moreover, the many surgical devices and techniques that have been introduced to this field of surgery in recent years contributed toward a reduction in morbidity and mortality [22,23]. Finally, the GDT protocol may be more useful in the intraoperative care of high-risk patients. Thus far, no definitive data exist to support this belief. Further trials are necessary before a definite conclusion can be made.

Many subsequent trials of the GDT protocol revealed results different from those of the original trial. The GDT for early sepsis patients is a good example. The first randomized controlled trial of GDT for early sepsis cases was performed by Rivers et al. [24] in 2001. More than a decade after their trial, three large multicenter trials investigated the validity of early GDT for managing early sepsis. The North American Protocol-Based Care for Early Septic Shock trial, the UK Protocolised Management in Sepsis (ProMISe) trial, and the Australasian Resuscitation in Sepsis Evaluation trial could not demonstrate a significant survival benefit for protocol-based early GDT over usual care at 90 days [25–27]. A meta-analysis of intraoperative goal-directed fluid therapy for elective major abdominal surgery also indicated that the benefits of GDT may not be as clear as had been suggested historically owing to the changes in the overall perioperative management of patients over time [28]. Based on an exploratory analysis, hypotensive patients experienced delayed bowel function. A decrease in the splanchnic blood flow during a hypotensive episode may lead to mucosal hypoxia and acidosis [7]. Experimental studies showed that the gastrointestinal mucosal pH decreases with reduction in blood flow [29]. In a clinical setting, postoperative ileus after surgical procedures may contribute to a delay in enteral nutrition, causing patient discomfort and prolonging hospitalization [30]. Certain limitations of this study are present. First, owing to the small number of episodes of hypotension than that reported previously, our sample size might have been too small to demonstrate differences between the two groups. Furthermore, our study only included low-risk patients; the benefits of GDT for those with a higher risk and severe comorbidities need to be evaluated. Finally, the intervention could not be blinded; however, the risk of bias was minimized by randomization; validated criteria for the primary outcome that was not subjective to observer bias; and the postoperative caregivers being unaware of the study assignment.

As compared to standard practice, PPV-guided GDT did not show significant advantages with respect to intraoperative hypotension, red blood cell transfusion, or postoperative complications during complex spine surgery.