Effects of Female Reproductive Hormone Levels on Inadvertent Intraoperative Hypothermia during Laparoscopic Gynecologic Surgery: A Retrospective Study

Background and Objectives: Female reproductive hormones may affect core body temperature. This study aimed to investigate the effects of female reproductive hormones on inadvertent intraoperative hypothermia in patients who underwent laparoscopic gynecologic surgery under general anesthesia. Materials and Methods: This retrospective study included 660 menstruating and menopausal female patients aged 19–65 years. The patients were divided into two groups according to the occurrence of inadvertent intraoperative hypothermia: non-hypothermia group (N = 472) and hypothermia group (N = 188). After propensity score matching, 312 patients (N = 156 in each group) were analyzed to investigate the association between intraoperative hypothermia and female reproductive hormones. As potential predictors of inadvertent hypothermia, the levels of female reproductive hormones were analyzed using binary logistic regression. Results: The association of estradiol (r = −0.218, p = 0.000) and progesterone (r = −0.235, p = 0.000) levels with inadvertent intraoperative hypothermia was significant but weakly negative before matching; however, it was significant and moderately negative after matching (r = −0.326, p = 0.000 and r = −0.485, p = 0.000, respectively). In a binary logistic analysis, the odds ratio for estradiol was 0.995 (p = 0.014, 0.993 < 95% confidence interval [CI] < 0.998) before matching and 0.993 (p = 0.000, 0.862 < 95% CI < 0.930) after matching, and that for progesterone was 0.895 (p = 0.000, 0.862 < 95% CI < 0.930) before matching and 0.833 (p = 0.014, 0.990 < 95% CI < 0.996) after matching. Conclusions: Estradiol and progesterone levels were associated with inadvertent intraoperative hypothermia. However, the odds ratio for female reproductive hormone levels was close to 1. Therefore, female reproductive hormones may not be a risk factor for hypothermia during gynecologic surgery under general anesthesia. However, a small sample size in this study limits the generalizability of the results.

Efficiency Evaluation of Neuroprotection for Therapeutic Hypothermia to Neonatal Hypoxic-Ischemic Encephalopathy

Background: To evaluate the safety and neurological outcomes of therapeutic hypothermia to neonatal hypoxic-ischemic encephalopathy (HIE).Materials and Methods: Medical records of 61 neonates with moderate to severe HIE were retrospectively enrolled and divided into a therapeutic hypothermia group (n = 36) and conventional therapy group (n = 25).Results: No significant difference in the incidence of severe adverse events was found between the two groups. Minimum and maximum voltages of amplitude-integrated electroencephalography (aEEG) recording results showed statistically significant differences in therapeutic hypothermia group after 72 h. The neonatal behavioral neurological assessment (NBNA) on the 28th day after birth and Bayley Scales of Infant Development, second edition (BSID II) scores at 18 months old were significant higher in the therapeutic hypothermia group than the conventional therapy group.Conclusion: Therapeutic hypothermia for neonates with moderate to severe HIE improved the development of the nervous system in 0–18-month-old infants and showed a predominant role in reducing death and major neuron development-associated disabilities.

Incidence of Severe Hypothermia and Its Impact on Postoperative Surgical Complications and Time Delay to Adjunct Treatments in Breast Surgery Cancer Patients: A Case-Controlled Study

Introduction: Unintended postoperative hypothermia frequently occurs upon arrival in the post anesthesia care unit (PACU). As part of our quality assurance program in anesthesia, we regularly monitor the incidence of this complication through our anesthesia information management system (AIMS). In this case-controlled retrospective study, our goal was to detect the incidence of unintended severe hypothermia in our breast surgery cancer patients, and subsequently to analyze the consequence of this complication in terms postoperative cutaneous infection, as well as its impact on further complementary treatment, such as radiotherapy and chemotherapy. Methods: This study was a retrospective analysis conducted through our AIMS system from 2015 through 2019, with extraction criteria based on year, type of surgery (breast), and temperature upon arrival in PACU. A tympanic temperature of less than 36 °C was considered to indicate hypothermia. Severe hypothermia was considered for patients having a temperature lower than 35.2 °C (hypothermic) (n = 80), who were paired using a propensity score analysis with a control group (normothermic) (n = 80) of other breast cancer surgery patients. Extracted data included time of surgery, sex, age, ASA status, and type and duration of the intervention. Results: The mean incidence of hypothermia was 21% from 2015 through 2019. The body mass index (BMI) was significantly lower in the hypothermia group before matching, 23.5 ± 4.1 vs. 26.4 ± 6.1 kg/m2 in normothermic patients (p < 0.05). The hypothermia group also had significantly fewer monitoring and active warming devices. No difference was noted for wound complications. Time to complementary chemotherapy and or radiotherapy did not differ between groups (52 ± 21 days in group hypothermia vs 49 ± 22 days in the control group). Conclusion: Severe intraoperative hypothermia remains an important quality assurance issue in our breast surgery cancer patients, but we could not detect any long-term effect of hypothermia.

Hypothermic treatment reduces matrix metalloproteinase-9 expression and damage in the liver following asphyxial cardiac arrest in rats

Background Hypothermic treatment is known to protect organs against cardiac arrest (CA) and improves survival rate. However, few studies have evaluated the effects of hypothermia on CA-induced liver damages. This study was designed to analyzed the possible protective effects of hypothermia on the liver after asphyxial CA (ACA). Rats were randomly subjected to 5 min of ACA followed by return of spontaneous circulation (ROSC). Body temperature was controlled at 37 ± 0.5 °C (normothermia group) or 33 ± 0.5 °C (hypothermia group) for 4 h after ROSC. Liver tissues were extracted and examined at 6 h, 12 h, 1 day, and 2 days after ROSC. Results The expression of infiltrated neutrophil marker CD11b and matrix metallopeptidase-9 (MMP9) was investigated via immunohistochemistry. Morphological damage was assessed via hematoxylin and eosin (H & E) staining. Hypothermic treatment improved the survival rate at 6 h, 12 h, 1 day, and 2 days after ACA. Based on immunohistochemical analysis, the expression of CD11b and MMP9 was significantly increased from 6 h after ACA in the normothermia group. However, the expressions of CD11b and MMP9 was significantly decreased in the hypothermia group compared with that of the normothermia group. In addition, in the results of H & E, sinusoidal dilatation and vacuolization were apparent after ACA; however, these ACA-induced structural changes were reduced by the 4 h-long hypothermia. Conclusions In conclusion, hypothermic treatment for 4 h inhibited the increases in CD11b and MMP9 expression and reduced the morphological damages in the liver following ACA in rats. This study suggests that hypothermic treatment after ACA reduces liver damages by regulating the expression of CD11b and MMP9.

HSP70-mediated neuroprotection by combined treatment of valproic acid with hypothermia in a rat asphyxial cardiac arrest model

It has been reported that valproic acid (VPA) combined with therapeutic hypothermia can improve survival and neurologic outcomes in a rat asphyxial cardiac arrest model. However, neuroprotective mechanisms of such combined treatment of valproic acid with hypothermia remains unclear. We hypothesized that epigenetic regulation of HSP70 by histone acetylation could increase HSP70-mediated neuroprotection suppressed under hypothermia. Male Sprague-Dawley rats that achieved return of spontaneous circulation (ROSC) from asphyxial cardiac arrest were randomized to four groups: normothermia (37°C ± 1°C), hypothermia (33°C ± 1°C), normothermia + VPA (300 mg/kg IV initiated 5 minutes post-ROSC and infused over 20 min), and hypothermia + VPA. Three hours after ROSC, acetyl-histone H3 was highly expressed in VPA-administered groups (normothermia + VPA, hypothermia + VPA). Four hours after ROSC, HSP70 mRNA expression levels were significantly higher in normothermic groups (normothermia, normothermia + VPA) than in hypothermic groups (hypothermia, hypothermia + VPA). The hypothermia + VPA group showed significantly higher HSP70 mRNA expression than the hypothermia group. Similarly, at five hours after ROSC, HSP70 protein levels were significantly higher in normothermic groups than in hypothermic groups. HSP70 levels were significantly higher in the hypothermia + VPA group than in the hypothermia group. Only the hypothermia + VPA group showed significantly attenuated cleaved caspase-9 levels than the normothermia group. Hypothermia can attenuate the expression of HSP70 at transcriptional level. However, VPA administration can induce hyperacetylation of histone H3, leading to epigenetic transcriptional activation of HSP70 even in a hypothermic status. Combining VPA treatment with hypothermia may compensate for reduced activation of HSP70-mediated anti-apoptotic pathway.

Comparison of Uncontrolled and Device-Induced Therapeutic Hypothermia in Newborn Infants with Hypoxic Ischemic Encephalopathy

Background. Newborn infants who have undergone severe birth asphyxia have a high risk of neurological disorders and death. The most effective method for the treatment of hypoxic ischemic encephalopathy caused by intrapartum asphyxia is therapeutic hypothermia, or targeted temperature management. Currently, there are no large studies comparing its different methods, therefore the aim of our study was to compare the effectiveness of device-induced and uncontrolled therapeutic hypothermia in newborn infants who underwent intrapartum asphyxia.Materials and methods. Study design: we conducted a retrospective, longitudinal, cohort study in 39 newborn infants born in severe asphyxia and receiving uncontrolled therapeutic hypothermia (group 1), and in 48 newborn infants born in severe asphyxia and receiving device-induced therapeutic hypothermia (group 2). Statistical data processing was carried out using standard techniques.Results. The body temperature in newborn infants of both groups was reduced to 33.5 °C within the first hour, but when using uncontrolled therapeutic hypothermia, the body temperature fluctuated from 32 to 35 °C. Device-induced therapeutic hypothermia has a more effective neuroprotective effect as compared to uncontrolled hypothermia (p< 0.05) and more rapidly stabilizes metabolism in newborns due to a decrease in lactate levels (p < 0.05). In newborns device-induced therapeutic hypothermia stabilizes hemodynamics more quickly compared to uncontrolled therapeutic hypothermia (p < 0.05). Device-induced therapeutic hypothermia reduces the period of hospitalization in the neonatal intensive care unit (p < 0.05), the risk of cerebral edema (p < 0.05) and of the repeated episodes of seizures (p < 0.05). Conclusion. Using uncontrolled therapeutic hypothermia causes a high risk of unintentional fluctuations in rectal temperature towards both hypothermia and rewarming, which can aggravate the severe condition of newborn infants. Device-induced therapeutic hypothermia has a more effective neuroprotective effect.

Correlation between the Perfusion Index and Intraoperative Hypothermia: A Prospective Observational Pilot Study

Background and Objectives: We examined the association between the baseline perfusion index (PI) and changes in intraoperative body temperature during general anesthesia. The PI reflects the peripheral perfusion state. The PI may be associated with changes in body temperature during general anesthesia because the degree of redistribution of body heat from the central to the peripheral compartment varies depending on the peripheral perfusion state. Materials and Methods: Thirty-eight patients who underwent brain surgery were enrolled in this study. The baseline PI and body temperature of the patients were measured on entering the operating room. Body temperature was recorded every 15 min after induction of anesthesia using an esophageal temperature probe. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for intraoperative hypothermia. Results: Eighteen patients (47 %) developed hypothermia intraoperatively. The baseline PI was significantly lower among patients in the hypothermia group (1.8 ± 0.7) than among those in the normothermia group (3.0 ± 1.2) (P < 0.001). The baseline PI and body temperature were independently associated with intraoperative hypothermia (PI: odds ratio [OR], 0.270; 95% confidence interval [CI], 0.105–0.697; P = 0.007, baseline body temperature: OR, 0.061; 95% CI, 0.005–0.743; P = 0.028). Conclusions: This study showed that low baseline PI was the factor most related to the development of intraoperative hypothermia. Future studies should consider the PI as a predictor of intraoperative hypothermia.

Rewarming rats at 37˚C rescues hypothermia with significant changes in IL-1β levels in the intestinal tissue and blood

Background Hypothermia secondary to accidental exposure is becoming increasingly prevalent in the general population; however, the mechanisms and early treatments of hypothermia require additional study. Methods A hypothermia-rewarming SD rat model was established by immersing rats in 15˚C seawater for 5h and then rewarming at 37˚C for 2, 6 and 12 h. The rats were randomly divided into a normal control group (group C), hypothermia group (group H) and rewarming group (group R). The changes in the levels of inflammatory factors and pathophysiology of the intestinal tissues of rats were assessed. The blood was collected in test tubes, and the levels of cytokines in the separated plasma were detected using ELISA. The intestinal tissue was ground and lysed, and protein expression profiles of 67 inflammatory factors were measured using a protein chip. These samples were further subjected to reverse transcription-quantitative (RT-q)PCR analysis and tissue section staining. Results The temperature of the abdomen and the physiological state of the rats was significantly altered during immersion in the hypothermic seawater, and returned to normal after rewarming. The protein chip showed that inflammatory factors, including IL-1β, IL-10 and IL-6, were differentially expressed in the intestine. Using ELISA, it was shown that IL-1β, IL-6 and IL-10 levels were also upregulated in the plasma. Comparing the ratios of IL-1β to IL-6 and IL-1β to IL-10, IL-1β was found to be significantly more upregulated compared with IL-10 and IL-6 in the intestine during hypothermia. The immunohistochemical staining of IL-1β showed that IL-1βexpression first increased then decreased during the rewarming period, and similar results were obtained based on RT-qPCR analysis. Conclusion Rewarming at 37˚C may be a suitable method for early treatment of hypothermia, and IL-1β may serve as a potential biomarker for assessing the severity of hypothermia.

Effect of Hypothermia on Serum Myelin Basic Protein and Tumor Necrosis Factor-α in Neonatal Hypoxic-Ischemic Encephalopathy

Objective Multiple randomized controlled trials have shown that hypothermia is a safe and effective treatment for neonatal moderate or severe hypoxic-ischemic encephalopathy (HIE). The neuroprotective mechanisms of hypothermia need further study. The aim of this study was to investigate the effect of hypothermia on the serum levels of myelin basic protein (MBP) and tumor necrosis factor-α (TNF-α) as well as neurodevelopmental outcomes in neonatal HIE. Study Design Eighty-five neonates with moderate-to-severe HIE were divided into a hypothermia group (n = 49) and a control group (n = 36). Serum levels of MBP and TNF-α within 6 hours after birth and after 3 days of treatment were determined by enzyme-linked immunosorbent assay, and neurodevelopmental outcome at the age of 12 to 15 months was assessed by using the Gesell development scale. Results After 3 days of treatment, serum levels of MBP and TNF-α in the control group were not significantly different from levels before treatment (p > 0.05), and serum levels of MBP and TNF-α in the hypothermia group were significantly lower than levels before treatment (p < 0.05). Serum levels of MBP and TNF-α were significantly negatively correlated with developmental quotient (DQ; r = − 0.7945, p = 0.0000; r = − 0.7035, p = 0.0000, respectively). Serum levels of MBP and TNF-α in neurodevelopmentally impaired infants were significantly higher than those in infants with suspected neurodevelopmental impairment and those in neurodevelopmentally normal infants (both p < 0.01). The rate of reduction of neurodevelopmental impairment was higher among infants in the hypothermia group than among those in the control group (χ2 = 16.3900, p < 0.05). Conclusion Hypothermia can reduce serum levels of MBP and TNF-α in neonates with HIE. Inhibiting the release of TNF-α may be one of the mechanisms by which hypothermia protects the myelin sheath. Key Points

Effects of selective intracarotid cerebral hypothermia on the size of ischaemic stroke in an experiment

<p><strong>Background.</strong> Ischaemic stroke is one of the leading causes of death and disability worldwide. Selective intracarotid cerebral hypothermia is one of the promising methods to prevent ischaemic stroke. However, currently available studies do not allow us to conclude the effectiveness of applying this method in humans and assess its effect on the system temperature.</p><p><strong>Aim.</strong> To investigate the effect of selective intracarotid cerebral hypothermia on the size of ischaemic stroke in large pigs, determining the optimal period of hypothermia and the severity of the effects of intracarotid hypothermia on the system temperature.</p><p><strong>Methods.</strong> The study was conducted on mini-pigs weighing 30–70 kg and included two stages. During the first stage, pigs were divided into two groups: control (n = 4) and intracarotid hypothermia for 3 h, exciting periods before and after reperfusion (n = 2). During the second stage, animals were also divided into two groups: hypothermia group within 1.5 h before reperfusion (n = 2) and hypothermia group within 1.5 h after reperfusion (n = 2). The technique for modelling ischaemic stroke was the same as in all groups and consisted of frontotemporal craniotomy and compression of the middle cerebral artery for 3 h. Intracarotid hypothermia was performed by infusing + 4 °C NaCl solution in the ascending pharyngeal artery. At 48 h after starting the experiment, a brain magnetic resonance imaging scan was performed to determine the size of the stroke.</p><p><strong>Results.</strong> The mean size of the stroke focusing in the control group was 10.75%, in the hypothermia group before reperfusion (10.95%) and in the hypothermia group after reperfusion (1.65%) of the volume of the cerebral hemisphere. The stroke size in the hypothermia group for 3 h could not be determined due to complications that developed in animals intraoperatively and postoperatively. The effect of intracarotid hypothermia on the systemic temperature in an animal weighing 65 kg was 0.4 °C.</p><p><strong>Conclusion.</strong> Based on the study results, a marked decrease in the focus of ischaemic stroke was found with the use of intracarotid hypothermia within 1.5 h after reperfusion. Intracarotid hypothermia was found to do not have a pronounced effect on the system temperature.</p><p>Received 2 May 2020. Revised 20 May 2020. Accepted 25 May 2020.</p><p><strong>Funding:</strong> The work is supported by a grant of the Russian Foundation for Basic Research (project No. 18-415-540025).</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p><p><strong>Author contributions</strong><br />Conception and study design: E.I. Fartakov, V.V. Lomivorotov, E.I. Kretov, A.R. Tarkova<br />Data collection and analysis: D.U. Malaev, A.A. Boykov, A.A. Prokhorikhin, D.V. Volchenko, I.S. Zykov, P.O. Seleznev<br />Drafting the article: E.I. Fartakov, D.U. Malaev, A.R. Tarkova<br />Critical revision of the article: E.I. Kretov, V.V. Lomivorotov, V.I. Baystrukov, N.I. Grachev, D.S. Sergeevichev, A.M. Chernyavskiy<br />Final approval of the version to be published: E.I. Fartakov, V.V. Lomivorotov, D.U. Malaev, A.R. Tarkova, A.A. Boykov, <br />A.A. Prokhorikhin, D.V. Volchenko, I.S. Zykov, P.O. Seleznev, V.I. Baystrukov, N.I. Grachev, D.S. Sergeevichev, A.M. Chernyavskiy, E.I. Kretov</p>