A novel thermal compression device for perioperative warming: a randomized trial for feasibility and efficacy

The trial was designed according to CONSORT standards (see Fig. 1). Inclusion criteria included breast surgery under general anesthesia with an esophageal temperature probe, length of surgery for more than 30 min, legs fitting the sleeve dimensions of the device, two accessible legs and no contraindications to heating or compression of the lower legs. Recruitment occurred at Stanford University hospital from October 2014–March 2015. Randomization was done on a 1:1 ratio using a blocked randomization method and computerized number generator [23]. The elective breast surgery list was obtained weekly and the randomization was performed for that week. The block size was different each week and was dependent on the number of patients booked for surgery. The research assistant collecting the data was blinded to the randomization until the night before and the anesthesiologist and surgeon where blinded until they saw the patient in the preoperative bay. All people in the treating team were blinded to the randomization process. In the second stage of the study, using the same method, cases were assigned to either sole of the foot only or popliteal fossa only. Patients in all groups were operated in the supine position, received other standard of care measures including warmed blankets, warmed aesthetic gases, warmed intravenous fluids, and a thermal under warming mattress (Maxi-Therm Lite, 42 °C, Cincinnati Sub-zero, Cincinnati, USA) in the operating room. The operating room temperature was regulated between 21 and 23 °C. All patients received systemic antibiotic therapy on induction.

For this group an investigational prototype thermal compression device was used. The device is placed on the patient in the preoperative bay during completion of the preoperative checklist, during which sequential compression devices are routinely placed on the patient, and is switched on for use for at least 30 min preoperative depending on the waiting time for transfer to the operating room. A more detailed technical description is included in Additional file 1. The device has 150 mm × 200 mm warming pads driven by resistive heating with a temperature probe held against the skin that feeds back to a controller unit to ensure the skin temperature is limited at 43 °C. The warming system is a closed loop control system where a temperature set point can be selected on the control unit and closed loop feedback and control occur between the temperature probe, control unit, and warming blanket. This allows the system to adjust the warming blanket temperature to ensure the delivery of appropriate thermal energy to the site for maximum warming while preventing any undesired complications due to the delivery of excess heat. Each warming site utilized a separate system with individual closed loop heating control to account for differences in warming blanket positioning, heat transfer, and other differences between the sites. The heating elements are fitted within pockets of sleeves that are then strapped in close contact to the patient in the popliteal fossa and sole of the foot. There is also a sequential pneumatic calf compression sleeve component fitted to the patient’s lower legs in between the two heating areas. Leads from the two heating areas and one compression unit feed via cables to a mobile controller unit that can be transported with the patient. Figure 2 displays an artistic rendition of the prototype device identifying the areas of heating and compression within the lower leg sleeve. In the operating room FAW (Bair Hugger, 3 M, St Paul USA) was placed on the body from the surgical preparation area site (upper abdomen) down but not turned on. One patient was excluded due to failure of the thermal under warming mattress at the beginning of surgery; another was excluded due to not having leg compression (discussed below).

These patients had the current standard of care at Stanford Hospital with FAW (Bair Hugger Model 750, blanket Full Body, High setting (43 +/− 3 °C), 3 M, St Paul USA) placed on the body from the surgical preparation area site (upper abdomen) down and including the feet and activated as soon as possible once inside the operating room. The FAW blanket was removed after extubation and prior to transport of the patient to the PACU. FAW patients also had pneumatic sequential compression devices (Kendall SCD, Covidien, Mansfield, USA) placed as prophylaxis for deep venous thrombosis while in the operating room. No patients were excluded.

To understand the effect of individual heating areas, patients were randomized to groups with single heating areas only using the same above described process. Each group received the same interventions and standard of care as the device group in stage I but one group (9 patients) had only the popliteal fossae heated (popliteal group) while the other group (9 patients) was heated only with the sole of the feet (sole group). As the FAW group from stage I is the current standard of care at Stanford University Hospital, we intended to compare the results of those patients recruited in stage 2 with the results of the patients in the FAW group of stage I. Early feedback to the investigators from the attending anesthesiologists were that they were observing patients in these groups were needing to have the FAW activated often so we analyzed the results of this stage after our intended half way point (18 patients, 9 in each group). There was one (of nine) patient in the popliteal and two (of nine) patients in the sole groups that had their intraoperative temperature rescued, because of intraoperative hypothermia, using FAW. The incidence of perioperative hypothermia in the popliteal group (44%, p = 0.16) and sole group (55.6%, p = 0.39) and as it was not significantly different to FAW (72%) it was decided to no longer recruit into this stage.

Our primary outcomes were perioperative temperatures and IPH incidence. Core temperature was estimated using a tympanic thermometer (Genius 2, Covidien. USA) during the whole perioperative period and measured, under anesthesia, using an esophageal temperature probe (placed 30-35 cm into the esophagus). Temperature at the skin was measured using a direct thermometer (Sure Temp Plus, Welch Allyn, USA). In the event that intraoperative hypothermia occurred in any of the device groups, it was up to the attending anesthesiologist, on a case by case basis, whether the FAW was turned on. Our secondary outcomes were local skin temperature, general and thermal comfort scores, intraoperative blood loss and presence of perioperative complications (including arrhythmia, post-operative seroma and wound infection). Thermal comfort was assessed using a visual analogue scale from −10 (uncomfortably cold) to 0 (comfortable) to 10 (uncomfortably warm). General comfort was assessed using a visual analogue scale from 0 (as uncomfortable as imaginably possible) to 10 (as comfortable as imaginably possible). Blood loss was recorded from the post-operative case note. Patients were also visited on the next post operative day prior to discharge. The anesthetic chart and medical notes where read retrospectively three months after the surgery for the presence of perioperative complications. The surgeons reviewing the patients postoperatively were blinded to which group the patient belonged to.

Calculations were made with STATA version 13. A two-tailed paired T test compared means in temperature with post hoc Bonferroni corrections. Pearson’s Chi squared test for goodness of fit was used to compare incidence of hypothermia. The correlation of esophageal and tympanic temperature measurements was analyzed using least squares regression analysis with Pearson’s correlation coefficient. Relative risk was used to calculate the risk of postoperative wound complications in patients who had postoperative hypothermia. Sample sizes were determined using a predicted efficacy of each group calculated with a minimum α of 0.05 and β of 0.8 for the primary outcomes involving temperature measurement (perioperative temperatures during each phase of surgery and IPH incidence). We took the lower incidence of IPH in large cohorts using FAW to have been reported as 60% [1‐3].. We made the assumption for an incidence of IPH in the full device arm to be 20%. Our calculation gave us a cohort of 18 patients in each treatment arm. Power was achieved in all reported outcomes except those mentioned.

The perioperative temperatures are displayed in Fig. 3 and Table 2. Mean temperatures in the full device group were significantly higher than the FAW group in the pre-operative, intraoperative and postoperative periods. The incidence of perioperative hypothermia (core temperature below 36 °C) in the full device group was 16.7%. This was significantly lower than the incidence in the FAW group which was 72% (p = 0.001). There was one patient in the full device group that received the FAW shortly after induction of anesthesia at the bequest of the attending anesthesiologist. There was also a significant difference in the incidence of post-operative hypothermia with the device, having a lower incidence compared to the FAW group (0% vs 22.2%, p = 0.03).

One patient had a unilateral mastectomy with the full device but then was required to have the contralateral side removed at a later date where she was randomly allocated to the FAW group. This allowed the comparison of the full device directly with the FAW within the same patient undergoing the same operation. Her perioperative temperatures are displayed in Fig. 4.

One patient in each group of stage I underwent reconstruction of the breast following mastectomy with a pedicled latissimus dorsi flap. The mean temperatures are displayed in Fig. 5. The full device was able to maintain normothermic temperatures throughout the perioperative period compared to the FAW patient that arrived in the post anesthesia care unit hypothermic (35.7 °C) and continued with FAW until discharge from the PACU.

The preoperative thermal comfort scores were higher in the full device group (1.1 +/− 0.4) compared to the FAW group (−0.3 +/− 0.2), although the difference was small (p < 0.001). There was a mild benefit over the popliteal group (0.7 +/− 0.2) (p < 0.01) while the sole group had a wide range (−0.6 +/− 1.0) (p < 0.001). The postoperative thermal comfort scores showed a similar small benefit for the full device group (0.8 +/− 0.2) compared to the FAW (−0.1 +/− 0.2) (p < 0.001) and similar results in the popliteal (0.8 +/− 0.2) (p = 1.0) and sole groups (1.6 +/− 0.8) (p = 0.06). There were no or mild differences in preoperative general comfort scores between the full device (8.8 +/− 0.2), FAW (9.0 +/− 0.3) (p = 0.08), popliteal (8.4 +/− 0.2) (p < 0.01) or sole (8.0 +/− 0.6) (p = 0.01) groups. There were also no or mild differences in postoperative general comfort scores between the full device (8.0 +/− 0.3), FAW (8.0 +/− 0.5) (p = 1.0), popliteal (7.4 +/− 0.2) (p < 0.01) or sole (7.1 +/− 0.6) (p < 0.01) groups. Of interest was that patients who reported a cold preoperative thermal score were more likely to develop perioperative hypothermia (p = 0.03).

The mean estimated blood loss was significantly less in the full device group (106.9 +/− 20.2) compared to the FAW group (130.3 ml +/− 20.8) (p = 0.002). There were four wound infections in the FAW group including one abscess requiring drainage, one cellulitis requiring admission and intravenous antibiotics and two superficial wound infections requiring oral antibiotics. The full device group had a single infective complication, a case of superficial wound infection requiring oral antibiotics. There were two cases of seroma in the FAW group, none in the full device group. Overall, patients in the FAW group had higher rates of hypothermia associated wound complications (27.8%) than those with the full device (5.6%) although, given the small sample size, the difference was not statistically significant (p = 0.07). When the patients were analyzed according to whether or not they became hypothermic in the PACU, regardless of whether they were in the full device, the FAW, the popliteal group or the sole group they were significantly more likely (57.1%, 4 of 7) (p = 0.001) to develop postoperative wound complications compared to normothermic patients (8.5%, 4 of 47). That is, if a patient became hypothermic in the PACU, they were more likely to develop a wound complication, independent of the group they were in. The risk of developing a wound complication was more than 6 times higher if the patient was hypothermic in the postoperative period (RR = 6.71, 95% Confidence Intervals 0.11–0.86, p < 0.001). There was one tissue expander associated wound dehiscence in the device group. There were no cases of thermal injury.

The mean temperatures of all groups are displayed in Fig. 6. Patients in the full device group had significantly higher intra-operative temperatures within the first 60 min and lower incidence of perioperative hypothermia then both the popliteal and sole groups. Heating in only the popliteal fossa or sole of the feet regions led to significantly higher mean temperatures in the pre-operative period compared to FAW, but not significantly different intraoperative or post-operative temperatures. The incidence of perioperative hypothermia in the popliteal group (44%, p = 0.16) and sole group (55.6%, p = 0.39) was not significantly different to FAW (72%). There was one (of nine) patient in the popliteal and two (of nine) patients in the sole groups that had their intraoperative temperature rescued using FAW.

We had one case, excluded from the cohort, which was found to not have the sequential calf compression turned on during the time out prior to surgery. This was realized intraoperatively and corrected. This then led to an increase in core temperature which is displayed in Fig. 7.

Our study is a proof of concept of the potential usefulness of this device with statistically significant improvements in mean temperature and incidence of perioperative hypothermia, in each stage of surgery. Importantly, the full device showed benefit in the early intraoperative period, during which redistribution hypothermia occurs. Our research suggests that both areas of heating are needed for efficacy. Warming the peripheries preventatively is not necessarily a novel idea [10, 24]. It is the combination of the heating locations with lower leg compression that is unique. Further studies with larger cohorts, in other patient groups with large surgical exposure, will be useful to further investigate the clinical significance of improved perioperative temperatures with this device. Our study also suggests, in one patient, that the compression is essential for efficacy. Having a treatment group using the full device without compression would have been conducting practice against international guidelines for preventing peri-operative deep venous thrombosis [25, 26].

Reconstruction of the breast following mastectomy with a pedicled latissimus dorsi flap involves standing uncovered before surgery for reconstructive mark up, multiple turns during surgery between supine and prone as well as large parts of the body exposed. FAW is even more difficult under these circumstances. The full device was able to maintain normothermic temperatures in this setting despite twice undergoing complete undraping and repreparation of the surgical site. The FAW by comparison only had undraping and repreparation performed once but was hypothermic on arrival and at discharge from the PACU.

There are a number of opportunities for heat loss. Patients are poorly insulated in cold waiting areas. In the operating room they are naked, exposed and prepared with cold sterilization liquids. At anesthetic induction, impairment of the normal autonomic thermoregulatory controls causes vasodilatation and reduction in muscle tone leading to redistribution hypothermia as cold peripheral blood is circulated to the warm core within the first 30 min of induction [10, 27]. Our study also found that a patient reporting a preoperative cold thermal score was associated with IPH. A patient’s feeling of cold preoperatively may indicate that additional warming measures should be taken prior to being declared ready for transfer.

There is a lack of research to explain when the most critical period is for maintaining normothermia, but research supports that if IPH occurs it leads to poor outcomes [1, 5, 6]. Research also supports that even if normothermic, core temperatures further below 37 °C lead to poorer outcomes [28]. IPH should be avoided at all times and temperatures closest to 37 °C should be the aim for all phases of surgery. In the United States, compliance with the standards set by the Joint Commission and the Centers for Medicare and Medicaid Services is obtained if the patient is normothermic at the end of anesthesia (when the patient leaves the PACU) or if the patient received FAW. Compliance is therefore still possible with IPH or with FAW implemented incorrectly [29]. This leads to high compliance with standards but no improvement in clinical outcomes. The challenge for these governing bodies is to create standards for perioperative temperature measurement that, when complied with, lead to better clinical outcomes.

The device group had a trend towards a lower incidence of post-operative wound infections compared to the FAW group, although we recognize the study was not powered to detect this difference and a larger cohort is needed to determine its true effect. Incidence of hypothermia occurring in the PACU has already been shown to be a risk factor for wound infection with a relative risk of 6.0 [28]. This is comparable to the relative risk (6.0) of not giving perioperative antibiotics within 2 h before the surgery start time [28]. Our study showed that hypothermia in the postoperative period increased the risk of developing associated postoperative wound complications (infection or seroma) by 6.7 times compared to those without postoperative hypothermia. This may be partially explained by the direct correlation between core temperature and production of reactive oxygen intermediates by polymorphonuclear leucocytes [30]. Patients who do not receive active warming also have reduced lymphocyte activation and reduced IL1b and IL2 levels, compared to those that do [31]. There were less, but not significant, estimated blood losses in the device group compared to the FAW group in our study, and there was a higher incidence of post-operative seroma in the FAW group. In a meta-analysis, incidence of IPH increases the relative risk of transfusion by 22% [32]. Activated partial thromboplastin time and prothrombin time are prolonged in patients with lower temperatures, even if the patient is normothermic. There is an improvement in clotting that occurs as temperature increases up to 37 °C, with no significant additional benefit above 37 °C. Laboratory parameters are measured at 37 °C meaning abnormalities in clotting will not be detected when measured in hypothermic patients [33]. Active warming has also been tied to reduced cardiac morbidity and reduced length of stay in hospital [5, 34]. There were no incidences of cardiac morbidity in any of our cohorts. A larger powered cohort would be useful to further investigate whether the device’s higher mean temperatures and lower incidence of hypothermia lead to a reduction in other hypothermia associated complications.

A number of usability issues have been identified with FAW [7]. FAW obstructs the surgical site, especially in surgery of the core [7]. Because FAW relies on conduction and convection for heat transfer, a larger surface area is required for efficacy which is difficult in procedures involving the core. Current FAW require a conscious decision to implement. This requires the clinician to “opt in” to prevent perioperative hypothermia. A thermal compression device, tied to the implementation of sequential compression devices which are already placed routinely, will make it easier for compliance.

To date, all available alternatives to FAW rely on surface area coverage and therefore contain the same intrinsic disadvantages [35]. The only exception to this is a novel device using a vacuum in conjunction with heating of the palms of the hand of a single upper limb which failed to show benefit over the FAW [28, 36]. In addition, this device requires the inconvenience of immobilizing one upper limb and obstructs its intravenous access [28, 35]. In our study, the thermal compression device also demonstrated higher levels of thermal comfort and equivalent levels of general comfort. This can also be achieved with pre-operative FAW [12].

Since direct core heating is not possible, heating major blood vessels of the limbs, like the popliteal, can be effective [36]. These vessels remain close to the surface in patients with elevated body mass index. The blood flow through the popliteal fossa during rest is around 200 mL/min and increases to around 500 mL/min during calf compression, sufficient to alter cardiac output measurements [37, 38]. This device takes advantage of the increased blood flow in the area during compression to act as a peripheral warming pump into the core. Heat applied to the sole of the foot takes advantage of heat transfer via arteriovenous anastomoses [24]. Our study shows that the both heating areas with leg compression are needed.