Intraoperative Thermoregulation Nursing CE Course

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Intraoperative Thermoregulation

Disclosure Statement

This learning activity aims to increase nurses' knowledge of thermoregulation during the intraoperative period, addressing the pathophysiology, risk factors, causes, complications, prevention and treatment of hypothermia, and the management of malignant hyperthermia. 

Upon the completion of this activity, learners will be able to:

• summarize the pathophysiology of thermoregulation and changes that occur after the administration of anesthesia
• identify the risk factors and causes of intraoperative hypothermia
• recognize complications of intraoperative hypothermia
• describe warming techniques to prevent or treat intraoperative hypothermia
• explain the presentation and treatment of malignant hyperthermia

Background

Hypothermia is the most common thermoregulation disturbance that occurs during surgical procedures. This can be attributed to the cold surgical environment, a decrease in activity, and anesthetic side effects. Patients may exhibit involuntary signs of hypothermia intraoperatively or postoperatively, such as shaking, shivering, and vasoconstriction. Patients may also experience malignant hyperthermia (MH), a rare inherited genetic disturbance that can occur during or after the administration of anesthetics (Diaz & Becker, 2010; Hinkle & Cheever, 2018).

Pathophysiology

Under normal circumstances, human body temperature is regulated through 3 processes: heat production, heat conservation, and heat loss. These processes are balanced to maintain a body temperature between 36.2 ˚C (97.2 ˚F) and 37.7 ˚C (99.9 ˚F). Temperatures within this range are considered normothermic. Despite this average, there are variations in temperature based on the body part and location of temperature assessment. The trunk of the body tends to have a higher temperature than the extremities. Core temperature (e.g., tympanic membrane temperature) tends to be 0.5 ˚C (0.9 ˚F) higher than surface temperature (e.g., oral temperature). Temperature can be influenced by metabolic and environmental changes and the time of day due to the influence of the circadian rhythm on body temperature. Over 24 hours, temperatures measured orally can fluctuate by 0.2 ˚C to 0.5 ˚C (0.36 ˚F to 0.9 ˚F). Ovulating individuals tend to have an even wider normal temperature range, as body temperature rises sharply before ovulation; this is the mechanism by which ovulation can be measured when using some family planning methods (McCance & Huether, 2019).

Hypothermia occurs when body temperature decreases below 36 ˚C (96.8 ˚F). There are different severities of hypothermia, as outlined in Table 1. Once the body temperature drops below 32˚C (89.6 ˚F), patient mortality rates increase to 21%. Hypothermia during the intraoperative period affects over 50% of surgical patients in the US (Association of Surgical Technologists [AST], 2019).

Table 1 

Severity of Hypothermia 

(AST, 2019)

Physics of Thermoregulation

The preoptic anterior area of the hypothalamus primarily manages thermoregulation. Information regarding the surface and core temperatures is obtained from peripheral thermoreceptors located in the skin and abdominal organs and central thermoreceptors in the spinal cord. This information is transmitted to the hypothalamus through a neural signal. If temperature levels decrease, the hypothalamus initiates heat production or heat conservation. If temperatures increase, the hypothalamus initiates mechanisms that lead to heat loss. Table 2 explains the possible mechanisms of heat production and heat loss (McCance & Huether, 2019).

Table 2

Mechanisms of Heat Production, Loss, and Conservation 

 (Diaz & Becker, 2010; McCance & Huether, 2019)

Effects of Anesthesia

Anesthetics have a proclivity to promote heat loss as well as eliminate the body's ability to initiate interventions to reduce heat loss. The administration of general or neuraxial anesthesia can affect thermoregulation. Patients who are under anesthesia without the intervention of artificial warming devices can become hypothermic, with their core temperature decreasing by 1˚ - 2˚ to 34.5˚C (94.1˚F). Volatile anesthetics such as halothane (Fluothane), isoflurane (Forane), desflurane (Suprane), and sevoflurane (Ultane); propofol (Diprivan); and older opioids (e.g., morphine sulfate [Duramorph] and meperidine [Demerol]) contribute to heat loss due to vasodilation. These drugs also act on the hypothalamus and impair its ability to initiate thermoregulation. They increase the heat-response threshold and lower the cold-response threshold by as much as 4˚C. Some medications affect thermoregulation to a lesser degree (e.g., nitrous oxide [INOmax] and ketamine [Ketalar]) or not at all (e.g., benzodiazepines such as midazolam [Versed], diazepam [Valium], lorazepam [Ativan]). Neuromuscular blocking agents (NMBAs) such as succinylcholine (Anectine), rocuronium (Zemuron), and vecuronium (Norcuron) do not cross the blood-brain barrier and therefore have no significant impact on temperature regulation (Diaz & Becker, 2010; Sessler, 2022).

General Anesthesia

After the administration of general anesthesia, body temperature decreases in 3 phases. The first phase—redistribution—occurs due to vasodilation, which allows warm blood to reach the cooler periphery, causing heat loss from the blood, which is then returned to the core at a lower temperature. Vasodilation is a direct result of anesthetic agents and the lowered threshold for vasoconstriction. This phase is known as redistribution hypothermia. Redistribution can last up to 3 hours and is the primary contributor to body heat loss during surgery. Phase 2, known as the linear phase, begins approximately 1 hour after anesthesia initiation and is due to decreased heat production from metabolism. This phase lasts approximately 2 to 4 hours, depending on the procedure length, and ends when temperatures reach 34.5 ˚C (94.1 ˚F). The amount of heat lost exceeds heat production, resulting in net heat loss. While general anesthesia is being administered, a patient's metabolic rate decreases by 15% to 40% (AST, 2019; Rauch et al., 2021; Riley & Andrzejowski, 2018). Heat loss during this phase occurs via:

• radiation due to temperature differences between the individual and the environment, which accounts for 40% of temperature loss
• convection due to the air currents and laminar flow (when all air in a space moves in a uniform direction at the same velocity) found in the operating room, which accounts for 30% of temperature loss
• evaporation due to the exposure of body cavities or mucous membranes, skin preparation, or the humidification of gases used during a surgical procedure, accounting for 25% of temperature loss
• conduction when the body encounters cold intravenous (IV) fluids or an operating table, which accounts for 5% of heat loss (Riley & Andrzejowski, 2018)

Once the linear phase ends, phase 3—the plateau phase—begins. During this phase, the core body temperature stabilizes and stays within a narrow range for the remainder of the surgical procedure (AST, 2019).

Neuraxial or Regional Anesthesia 

Unlike general anesthetics, neuraxial or regional anesthetics do not impair heat production. The most common neuraxial techniques include spinal, epidural, or a combination of the two. These types of anesthetics impair thermoregulation by lowering the shivering and vasoconstriction threshold in areas distal to the placement of the anesthesia. Vasodilation in the periphery causes a redistribution of cooler blood toward the core, decreasing the core body temperature. Compensatory mechanisms of vasoconstriction can occur above the level of the block in an attempt to maintain body temperature. The most significant risk of hypothermia occurs when neuraxial and general anesthesia are used together (Riley & Andrzejowski, 2018).

Risk Factors and Causes 

Many risk factors increase the likelihood of intraoperative hypothermia. Various causes of hypothermia are patient- and procedure-specific (McCance & Huether, 2019). Examples of risk factors include:

• age > 60 due to decreased subcutaneous fat, a lower metabolic rate, and lower resting muscle tone
• American Society of Anesthesiologists (ASA) physical status classification 2-5; the higher the grade, the higher the risk (see Table 3)
• hypothermia risk index score ≥ 4 (see Table 4)
• the presence of hepatic, thyroid, adrenal, or cardiac dysfunction
• preoperative temperature < 36.0 ˚C (96.8 ˚F)
• head injury
• infection with bacterial toxins
• spinal cord injury
• presence of burns
• traumatic injury
• an increased risk of cardiovascular complications
• low body mass index (BMI; ASA, 2020; AST, 2019; McCance & Huether, 2019; Riley & Andrzejowski, 2018; Yang et al., 2015)

Examples of causes of intraoperative hypothermia include:

• exposure of the body cavity
• operating room temperature below 23 ˚C (73.4 ˚F); operating room temperatures above 26 ˚C (78.8 ˚F) can decrease the prevalence of hypothermia but increases the risk of infection
• extended procedure length
• type of surgery; general surgery poses the highest risk due to an increased prevalence of these types of surgeries, the presence of an open abdominal cavity for several hours, the use of large amounts of room temperature saline solution for repeated lavage, blood loss, and fluid evaporation from the exposed mucosa
• use of an operating room with laminar airflow
• infusion of room temperature IV solutions
• administration of drugs that impair thermoregulatory mechanisms (see above)
• use of general and regional anesthesia
• inhalation of anesthetic agents that have not been warmed (AST, 2019; McCance & Huether, 2019; Riley & Andrzejowski, 2018; Yang et al., 2015)

Table 3

ASA Physical Status Classification 

(ASA, 2020)

Table 4

Hypothermia Risk Index 

(AST, 2019)

Temperature Monitoring

To prevent complications, patients undergoing surgery should have their core body temperature maintained at 35.5 ˚C (95.9 ˚F). Devices are utilized during the intraoperative period to monitor the patient's core temperature for hypothermia or hyperthermia. These devices help ensure the patient maintains a normothermic temperature. Any patient undergoing a surgical procedure that lasts longer than 30 minutes should be monitored for temperature changes; however, the standards for monitoring depend on which anesthesia organization's protocols the healthcare organization follows. Temperature monitoring is unnecessary when moderate sedation or a peripheral nerve block is used since the body's natural thermoregulation is unaffected (Sessler, 2022).

Temperature monitoring can take place at different body sites. Ideally, body temperature is monitored in highly perfused areas that provide an accurate measure of core temperature or a direct estimate of the core temperature that is accurate within 0.5 ˚C. Surgical patients should not have their temperature monitored via sites that indirectly estimate core body temperature. Ideal sites for measuring core temperature include the nasopharynx, distal esophagus, tympanic membrane via thermocouple, skin surface using a zero-heat-flux thermometer, or pulmonary artery. The distal esophagus gives an accurate reading of core body temperature; however, it is affected by the use of humidified gas if the temperature probe is not positioned correctly. Temperature measurement at this location is also inaccurate during surgeries that expose the thoracic cavity to ambient air. A nasopharyngeal temperature reading involves the insertion of the probe superior to the soft palate. This places the probe near the brain, giving an accurate core temperature reading. Nasopharyngeal monitoring is affected by inhaled gases. Measuring temperature using the pulmonary artery requires the insertion of a catheter to measure the temperature of circulating blood. This type of monitoring is invasive and expensive and is therefore reserved for use in circumstances that require close hemodynamic monitoring. The preferred intraoperative method is tympanic membrane monitoring with a thermocouple. These measurements are highly reliable and consistent due to the location of the tympanic membrane in relation to the hypothalamus and carotid artery. Circumstances when these monitoring sites are not accessible include when a facemask or supraglottal airway is used, when neuraxial anesthesia is administered, or during surgical procedures that affect the oral area or esophagus. In these cases, it is necessary to monitor the patient's body temperature using a near-core site such as the bladder, axilla, rectum, temporal artery, or tympanic membrane using an infrared sensor. Unfortunately, monitoring skin temperature does not accurately reflect core body temperature. Monitoring temperature via the external aural canal, rectum, temporal artery, and tympanic membrane using infrared monitoring also equates poorly to core body temperature during the intraoperative period (AST, 2019; Sessler, 2022).

Complications

Since most cellular functions are temperature-dependent, they are greatly affected by changes in body temperature. Changes in body temperature as little as 1 to 2˚C can cause coagulopathy, infection, prolonged effects of medications, shivering, and myocardial ischemia (Sessler, 2022).

Coagulopathy

Hypothermia interferes with coagulopathy by impacting different pathways. Hypothermia impairs platelet aggregation by hindering the release of thromboxane A2, which inhibits initial platelet plug formation, leading to coagulopathy. Platelets are kept in the portal circulation, liver, and spleen at reduced temperatures. This reduction of platelets in the systemic circulation leads to thrombocytopenia when temperatures reach between 25 ˚C (77 ˚F) and 30 ˚C (86 ˚F). Additionally, temperature-dependent enzymatic activity throughout the coagulation cascade is reduced when there is a decrease in body temperature. Clot formation is affected by this disruption in the cascade. The blood loss that occurs during surgery further exacerbates this decrease in clotting capability with the decrease in clotting factors. The combination of platelet and enzymatic dysfunction and loss of clotting factors leads to increased blood loss, likely to the point of needing a transfusion. A decrease of as little as 1˚C (1.8˚F) can lead to a total blood loss increase of up to 30%, which can also cause an increase in the need for a blood transfusion by up to 70%; therefore, the risk of needing a blood transfusion increases as both temperature decreases and exposure time increases (AST, 2019; Rauch et al., 2021; Sessler, 2022).

Identifying hypothermia-induced coagulopathy is difficult due to the temperature difference between the sample obtained, and the sample tested. Before testing, the sample is warmed to 37 ˚C (98.6 ˚F). At that temperature, the results would appear within the expected range. If testing were completed on the sample in a temperature-adjusted space, the coagulation changes would be identified (Rauch et al., 2021; Sessler, 2022). 

Infection

Surgical site infection (SSI) is the chief risk for postoperative patients and is the primary cause of nosocomial infections in this group. Hypothermia interferes with the body's ability to fight infection by decreasing tissue perfusion, cell mobility, and scar formation. The vasoconstriction that occurs as a natural response to cold to conserve body temperature reduces tissue perfusion in wounded areas. This decreased perfusion leads to impaired tissue oxygenation, which impairs wound healing. Decreased temperatures also slow the motility of the immune cells necessary for wound healing, including neutrophils, macrophages, and platelets. Hypothermia also hinders the activation of the innate immune system, T-cell-mediated defense, and antibody production. Hypothermia also inhibits scar formation, which is a necessary process to prevent wound dehiscence. Infection risk rises once body temperature decreases to ≤ 34.5 ˚C (94.1 ˚F). SSIs, as a result of hypothermia, increase costs and lengths of stay (Rauch et al., 2021; Sessler, 2022).

Prolonged Effects of Medications 

Medication pharmacokinetics are based on a normothermic temperature range. Drug pharmacokinetics is altered when a patient's body temperature decreases. Since hypothermia decreases enzyme activity and slows the rate of metabolism, drugs are not broken down and excreted properly and begin accumulating, prolonging their action. One example of this phenomenon is propofol (Diprivan). The liver metabolizes propofol (Diprivan), and hypothermia causes decreased hepatic blood flow. This leads to a decreased breakdown of propofol (Diprivan) and systemic accumulation. The concentration of fentanyl (Sublimaze) is similarly impacted by hypothermia. For every 1˚C (1.8 ˚F) decrease in core temperature, the concentration of fentanyl (Sublimaze) increases by 5%. Volatile anesthetics are also affected by temperature. At lower temperatures, the minimum alveolar concentration needed to inhibit a muscular response is lowered, leading to more tissue solubility, which can prolong their effects. This can delay a patient's emergence from anesthesia. NMBAs are highly susceptible to lower temperatures. The presence of hypothermia doubles the length of action of vecuronium bromide (Norcuron) and increases the duration of action of atracurium (Tacrium) by approximately 60% (Rauch et al., 2021; Sessler, 2022).

Cardiac Effects 

Hypothermia affects the myocardium. Decreased temperatures can reduce the left ventricle's contractibility, leading to decreased cardiac output. Hypothermia can also provoke atrial and ventricular arrhythmias. The initial arrhythmia seen is sinus tachycardia, but as body temperature decreases, the heart rate decreases until bradycardia emerges. Hypothermia also decreases the ability of hemoglobin to release oxygen into the tissues, which can lead to myocardial ischemia (AST, 2019).

Shivering

The shivering response happens at 1˚C below the threshold for vasoconstriction. Shivering does not occur during the intraoperative period since anesthesia inhibits the body's natural defenses against hypothermia. Once the anesthesia has worn off in the postoperative period, the shivering response returns. The effects of shivering include changing the metabolic rate and increasing postoperative pain. Shivering also increases oxygen consumption, which can further aggravate hypoxia and ischemia. Postoperative shivering can be treated with a one-time dose of 12.5 to 25 mg of meperidine (Demerol) IV. Alternative drugs for shivering include the alpha-2 agonists clonidine (Catapres) at 150 mcg or dexmedetomidine (Precedex) at 0.5 mcg/kg, which can be administered IV over 3 to 5 minutes (Sessler, 2022).

Prevention and Treatment

Thermoregulation is essential in preventing hypothermia, which affects all surgical patients who are not warmed through external intervention. Even patients who are artificially warmed undergo mild hypothermia due to heat redistribution. Core temperature decreases during the initial hour of anesthesia administration. After this time, body temperature can decrease further or increase based on room temperature and the adequacy of warming techniques. The surgical team determines which method is used, depending on the surgical procedure being performed, access to the surgical site, required access to IV sites, and patient positioning during the procedure. The prevention or treatment of hypothermia involves either passive or active warming. It is recommended that both types of warming should be used to decrease the extent of temperature loss (AST, 2019; Sessler, 2022).

Prewarming

Prewarming is a technique used to prevent hypothermia. This type of warming occurs in the pre-operative area and continues until the patient enters the surgical suite. Although prewarming cannot increase core body temperature, it does decrease the temperature gradient between the core and peripheral temperatures. This allows the core temperature to remain at least 0.4 ˚C warmer than the core temperature of patients who did not undergo prewarming. There is no evidence-based recommendation on how much time should elapse before beginning surgery prewarming. Prewarming utilizes the same active warming devices described below (AST, 2019; Rauch et al., 2021; Sessler, 2022).

Passive Warming

This type of warming focuses on decreasing heat loss by insulating the patient; it is the easiest method of warming. Passive warming prevents heat loss by covering the patient and any exposed skin as much as possible without hindering access to the surgical site. Insulation from heat loss can be obtained using warm or foil blankets, sterile drapes, and plastic coverings. Anesthesia providers often place a plastic covering over the patient's head to prevent heat loss. Insulation can reduce heat loss during surgery by 30%; however, when this method is used alone, patients still become hypothermic (AST, 2019; Rauch et al., 2021; Sessler, 2022).

Active Warming 

Active warming utilizes a device to warm the patient. Active warming techniques have been shown to decrease postoperative shivering, SSIs, and the need for blood transfusions compared to passive warming only (Sessler, 2022).

Forced Air Warming 

Forced air warming (FAW) is the most common technique used to heat patients during the intraoperative period when conventional surgical techniques are utilized. The FAW system takes air from the environment, heats it, and then blows the warm air over the patient utilizing a specific blanket. The patient is warmed via convection. A benefit of FAW is that it can be distributed over a large surface area. However, using FAW might disrupt the laminar airflow system employed during certain surgical procedures and can impact surgical site sterility and increase the prevalence of SSIs. Patients also have a risk of being burned when FAW is used (Ackerman et al., 2018; Sessler, 2022).

Resistive Heating 

This type of heating converts electrical energy into heat. The patient is warmed through conduction. An electrical current is passed through carbon polymer fiber strips, which generates heat. This heating technique can take an extended period to produce adequate warmth. Additionally, patients could sustain burns (Bindu et al., 2017).

Fluid Warming 

When fluid warming occurs, the fluid to be administered intravenously is warmed to between 38 ˚C (100.4 ˚F) and 40 ˚C (104 ˚F). Unfortunately, this method does not effectively increase body heat under normal circumstances. This is due to the time it takes for fluids to be administered: by the time the fluid reaches the patient, it has already cooled down because of the temperature in the operating suite. Also, IV fluids can only be warmed to a temperature that slightly exceeds the patient's core body temperature. Warming of fluid used for peritoneal lavage also does not transfer adequate heat to the patient. Fluid warming is needed to decrease the cooling effect that occurs when fluids at room temperature are administered, as each liter of fluid infused can decrease body temperature by 0.25 ˚C. Fluid warming is only effective at raising body temperature for patients receiving large amounts of IV fluids rapidly, such as those who are hemorrhaging; however, even this increase is minimal. Blood products are typically stored at 4˚C (39.2˚F). When blood is administered in large quantities, such as > 50 mL/kg/hr in adults, blood should be warmed prior to administration (Bindu et al., 2017; Matika et al., 2016; Sessler, 2022).

Malignant Hyperthermia 

MH is an inherited disorder of the skeletal muscles that predisposes a patient to a life-threatening adverse reaction (i.e., a fulminant MH event) in response to volatile anesthetics such as halothane (Fluothane), isoflurane (Forane), sevoflurane (Ultane), desflurane (Suprane), and the skeletal muscle relaxant succinylcholine (Anectine). MH affects an estimated 1 in 100,000 cases involving volatile anesthetics; however, this number is likely underestimated due to some patients exhibiting mild or atypical reactions. Signs and symptoms of MH consist of hypercarbia, tachycardia, tachypnea, arrhythmia, rigidity, elevated body temperature, unstable blood pressure, cyanosis, and dilated pupils (Hinkle & Cheever, 2018; National Organization for Rare Disorders [NORD], 2013; Rosenbaum & Rosenberg, 2022).

Treatment of MH involves discontinuing the triggering anesthetic agent and cooling the patient. Dantrolene sodium (Dantrium), a peripheral muscle relaxant, is used to inhibit the calcium release channel in skeletal muscles and is effective for treating and preventing fulminant MH. The patient will likely have their blood gas and metabolic profile checked (Hinkle & Cheever, 2018; NORD, 2013).

Intraoperative MH may prompt the termination of the surgery, as it is often due to administering anesthetic medications. The patient's airway must be maintained, and 100% oxygen at 10-15 L/min should be administered using a nonrebreather mask. If the patient is already intubated, mechanical ventilation should be used to maintain oxygenation. To decrease the patient's temperature, cooling agents such as iced 0.9% sodium chloride or a cooling blanket should be used. Nurses should assess the patient's urine output during treatment to ensure they produce at least 30 mL/hour (Hinkle & Cheever, 2018).

References 

Ackerman, W., Fan, Q., Parekh, A. J., Stoicea, N., Ryan, J., & Bergese, S. D. (2018). Forced-air warming and resistive heating devices. Updated perspectives on safety and surgical site infections. Frontiers in Surgery, 5(64). https://doi.org/10.3389/fsurg.2018.00064

American Society of Anesthesiologists. (2020). ASA physical status classification system. https://www.asahq.org/standards-and-guidelines/asa-physical-status-classification-system

Association of Surgical Technologists. (2019). AST guidelines for best practice in maintaining normothermia in the perioperative patient. https://www.ast.org/uploadedFiles/Main_Site/Content/About_Us/ASTGuidlinesNormothermia.pdf

Bindu, B., Bindra, A., & Rath, G. (2017). Temperature management under general anesthesia: Compulsion or option. Journal of Anaesthesiology Clinical Pharmacology, 33(3), 306-316. https://doi.org/10.4103/joacp.JOACP_334_16

Diaz, M., & Becker, D. E. (2010). Thermoregulation: Physiological and clinical considerations during sedation and general anesthesia. Anesthesia Progress, 57(1), 25-33. https://doi.org/10.2344/0003-3006-57.1.25

Hinkle, J. L., & Cheever, K. H. (2018). Brunner & Suddarth's textbook of medical-surgical nursing (14th ed.). Wolters Kluwer.

Matika, R., Ibrahim, M., & Patwardhan, A. (2016). The importance of body temperature: An anesthesiologist's perspective. Temperature, 4(1), 9-12. https://doi.org/10.1080/23328940.2016.1243509

McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). Elsevier.

National Organization for Rare Disorders. (2013). Rare disease database: Malignant hyperthermia. https://rarediseases.org/rare-diseases/malignant-hyperthermia

Rauch, S., Miller, C., Brauer, A., Wallner, B., Bock, M., & Paal, P. (2021). Perioperative hypothermia - A narrative review. International Journal of Environmental Research and Public Health, 18(16), 8749. https://doi.org/10.3390/ijerph18168749

Riley, C., & Andrzejowski, J. (2018). Inadvertent perioperative hypothermia. BJA Education, 18(8), 227-233. https://doi.org/10.1016/j.bjae.2018.05.003

Rosenbaum, H. K., & Rosenberg, H. (2022). Malignant hyperthermia: Diagnosis and management of acute crisis. UpToDate. Retrieved July 17, 2022, from https://www.uptodate.com/contents/malignant-hyperthermia-diagnosis-and-management-of-acute-crisis

Sessler, D. (2022). Perioperative temperature management. UpToDate. Retrieved December 7, 2022, from https://www.uptodate.com/contents/perioperative-temperature-management/print

Yang, L., Huang, C.-Y., Zhou, Z.-B., Wen, Z.-S., Zhang, G.-R., Liu, K.-X., & Huang, W.-Q. (2015). Risk factors for hypothermia in patients under general anesthesia: Is there a drawback of laminar airflow operating rooms? A prospective cohort study. International Journal of Surgery, 21, 14-17. https://doi.org/10.1016/j.ijsu.2015.06.079