The key clinical outcomes for HumiGard presented in the decision problem were:
incidence of hypothermia during and after surgery (defined as a core body temperature of less than 36°C)
incidence of surgical site infections
length of stay in post-operative recovery
total length of hospital stay
device-related adverse events
patient-reported pain.
The company carried out separate literature searches for laparoscopic and open surgery, encompassing both published and unpublished studies. Its submission included 24 studies, 20 involving laparoscopic surgery and 4 involving open surgery. The company used a checklist to determine if studies were generalisable and presented 16 (of the total 24) involving other humidification devices. The external assessment centre (EAC) considered that humidification systems other than HumiGard were beyond the scope of the evaluation and that those 16 studies should be excluded. The EAC's independent literature searches did not identify any additional studies on HumiGard. It judged that 7 studies provided relevant evidence: 5 on laparoscopic surgery (Herrmann and De Wilde 2015, Manwaring et al. 2008, Sammour et al. 2010, Yu et al. 2013 and Mason et al. 2016) and 2 on open surgery (Frey et al. 2012 and Weinberg et al. 2014).
Hermann and De Wilde (2015) reported on a double-blind randomised controlled trial that compared HumiGard with unwarmed, dry CO2 gas in patients aged 18 years or over with benign uterine diseases having gynaecological laparoscopic surgery. Randomisation led to 52 patients receiving warm (35±2°C), humidified (98% humidity) CO2 with HumiGard and 52 patients receiving standard room temperature, dry (0% humidity) CO2. The primary outcome was post-operative pain at 2, 4, 6, 24 and 48 hours as measured by a visual analogue scale (VAS). Secondary outcome measures were morphine consumption and demand and post-operative, patient-controlled analgesia, including rejected boli delivery (not delivered when request was made within 10 minutes of the previous bolus), temperature change during surgery, length of time spent in the recovery room and length of inpatient stay. The results showed a significant difference in total shoulder tip pain (p=0.037), which was one of a number pain outcomes and differences in some indicators of morphine consumption. There were no other statistically significant difference in any of the other outcome measures specified in the scope.
Manwaring et al. (2008) reported on a randomised controlled trial that compared HumiGard with unwarmed, dry CO2 gas in women aged 18 to 55 years having gynaecologic laparoscopic surgery. Randomisation led to 30 patients receiving warmed, humidified CO2 with HumiGard, and 30 patients receiving standard room temperature, dry CO2. The primary outcome was shoulder tip pain at 4 hours after surgery. Secondary outcome measures were time in recovery room, nausea, post-operative temperature and pelvic pain. The results showed a significant difference in change in core temperature from theatre to recovery (p=0.027) but no other statistically significant difference in the other outcome measures specified in the scope.
Sammour et al. (2010) reported a double-blind randomised controlled trial that compared HumiGard with unwarmed, dry CO2 gas in patients aged 15 years or older having elective laparoscopic colonic resection. Randomisation led to 41 patients receiving warm (37°C), humidified (98% humidity) CO2 with HumiGard, and 41 patients receiving room temperature, dry CO2. The primary outcome was total opiate analgesia used during inpatient stay. Secondary outcome measures were post-operative pain (measured on a VAS) at 2, 4, 8 and 12 hours and 1, 2, 3, 7, 14, 30 and 60 days after the operation. Other secondary outcome measures were intra-operative core temperature, cytokine response and length of inpatient stay. Six patients in the HumiGard group and 2 in the control group were excluded from the analysis with reasons given. The results showed that HumiGard had a significant effect on post-operative pain at rest on day 1 (p=0.01) and post-operative pain on moving on day 1 (p=0.018). The results showed no statistically significant difference in the other outcome measures specified in the scope.
Yu et al. (2013) reported on a double-blind randomised controlled trial that compared HumiGard with unwarmed, dry CO2 gas in children aged 8 to 14 years having an acute laparoscopic appendectomy. Randomisation led to 95 patients receiving warm (37°C), humidified (98% humidity) CO2 with HumiGard and 95 patients receiving room temperature, dry CO2. The primary outcome was post-operative pain (analgesic use) in the recovery room and at days 1 and 2 after the operation. Secondary outcome measures were pain intensity scores, intra-operative core temperature and post-operative recovery and return to normal activities. Two patients in the HumiGard group and 3 in the control group were excluded from the analysis with reasons given. The authors provided only graphical data for pain perceived at rest and on moving (VAS), but no differences were reported between the groups at any of the time points studied (0, 2, 4, 6, 8, 10, 12, 24 and 48 hours). The results showed no statistically significant difference in the other outcome measures specified in the scope.
Mason et al. (2016) was a retrospective cohort trial, done in a single UK centre, including patients having laparoscopic colorectal resections. The trial included 246 consecutive patients (mean age 68 years) with equal numbers having HumiGard or standard care. Outcome measures included incidence of surgical site infections, incidence of post-operative pneumonia, perioperative hypothermia, number of bed days, length of time in theatre recovery and cost. Body temperature was routinely measured tympanically on arrival to the post-anaesthetic recovery suite. The measurement of temperature intraoperatively was not standardised and therefore could not be included in the analysis. The results showed significant differences in perioperative hypothermia (p≤0.001), post-operative hypothermia on arrival in the recovery suite (p<0.001) and incidence of surgical site infections when hypothermic (p=0.02). There was a significant difference in overall incidence of surgical site infections (p=0.04) but not in length of hospital stay.
The EAC concluded that the clinical evidence on HumiGard for laparoscopic surgery was of relatively good quality: there are 4 randomised controlled trials and 1 retrospective cohort study in appropriate patients, all of which compared HumiGard with standard unwarmed, dry CO2 gas. However, the EAC also concluded that the cohort study (Mason et al. 2016) should be interpreted with caution, because of possible confounding factors arising from its design and uncertainty about the significance of its findings because of an incomplete description of regression and model development methods, regression diagnostics, any missing data and choice of final model.
Frey et al. (2012) reported on a randomised controlled trial that compared HumiGard with no insufflation in patients over 18 years (mean age 63.5 years) having elective open colonic surgery. Randomisation led to 42 patients receiving warm (37°C), humidified (100% humidity) CO2 gas with HumiGard and 41 patients receiving no insufflation. The primary outcome was intra-operative core and wound temperature and the secondary outcome measure was length of hospital stay. Two patients in the HumiGard group and 2 in the control group were excluded from the analysis with reasons given. The results showed significant benefits for the HumiGard group in terms of the proportion of patients with core temperature <36.0°C at end of surgery (p=0.005), the proportion of patients with core temperature <36.5°C at end of surgery (p=0.001), reduced core temperature at end of surgery (p≤0.001), reduced core temperature during surgery (p≤0.001), reduced wound area temperature during surgery (p≤0.001) and reduced wound edge temperature during surgery (p≤0.001). The results showed no statistically significant difference between the groups for length of stay.
Weinberg et al. (2014) reported on a prospective pilot randomised controlled trial published as an abstract that compared HumiGard and standard care (predetermined temperatures for infused fluid, ambient air and heating mattress temperature) with standard care alone in adult patients having primary orthotopic liver transplantation. No details were provided regarding number of patients in each group, but 22 patients were randomised to the intervention or control. The primary outcome was intra-operative core temperature before reperfusion and at completion of surgery. No secondary outcomes were reported. The core temperature immediately before reperfusion (°C, nasopharyngeal probe) was significantly higher in the HumiGard group (p=0.02). No statistically significant differences were reported for core temperature on wound closure (°C, nasopharyngeal probe), core temperature immediately before reperfusion (°C, pulmonary artery catheter), core temperature on wound closure (°C, pulmonary artery catheter), core temperature immediately before reperfusion (°C, bladder probe) and core temperature on wound closure (°C, bladder probe).
The clinical evidence submitted for open surgery was based on 2 small randomised controlled trials, 1 of which was a small pilot study published in abstract form only. The EAC concluded that there was insufficient information to critically appraise the Weinberg et al. (2014) abstract and Frey et al. (2012) was of reasonable quality.
Two randomised controlled trials involving laparoscopic abdominal surgery (Herrmann and De Wilde 2015, Sammour et al. 2010), included device-related adverse events as an outcome measure. Both studies reported no adverse events associated with the use of HumiGard. The other 3 studies on laparoscopic surgery did not report device-related adverse events. None of the studies on open abdominal surgery reported device-related adverse events.
The committee noted that there is good evidence that perioperative hypothermia is associated with poor patient outcomes, such as surgical site infections. Experts were in agreement and advised the committee that maintaining perioperative normothermia is now an established aim of clinical practice.
The committee considered that the clinical evidence supported the effectiveness of HumiGard in reducing hypothermia during laparoscopic and open abdominal surgery, noting that the evidence base was more substantial for laparoscopic surgery than for open surgery. The committee also noted the lack of high-quality direct comparisons supporting the use of HumiGard to avoid the adverse outcomes of hypothermia following surgery.
The committee noted that only 1 of the included studies involved children, and that in this study outcomes did not improve. The clinical experts advised that heat loss is partly determined by the ratio of body surface area to body mass. Because this is larger in children, overheating through the use of warming strategies can also be a concern. The committee concluded that there was insufficient evidence to recommend the use of HumiGard in children.
The committee heard from the clinical experts that total length of hospital stay after abdominal surgery has been reduced through the implementation of enhanced recovery programmes. Historically, length of stay after colorectal surgery was 7 to 9 days but this has now been reduced to approximately 4 to 5 days through the use of such programmes. This change makes it difficult to demonstrate how a single technology such as HumiGard affects total length of stay but the committee accepted that interventions which reduce surgical site infections would be beneficial.
The committee heard from the clinical experts that wound orientation is unlikely to affect the use and effectiveness of HumiGard. The committee was also advised that the presence of intra-abdominal sepsis would not be a barrier to its safe use.