Modelling hypothermia in patients undergoing surgery

Anesthesia causes substantial perturbation in the human heat balance. Nearly all patients administered anesthesia become hypothermic. Under normal physiological conditions, the core-to-peripheral temperature gradient is maintained by tonic vasoconstriction. By the induction of anesthesia, vasoconstriction is impaired. Hence, heat redistribution takes place from the warm core to the colder periphery, leading to hypothermia. The heat balance during cardiac surgery differs from most other surgery types in that the body is also actively cooled by means of a heart lung machine to provide extra protection to the heart and the brain. A drawback of rewarming with help of the heart lung machine is that heat is transferred to the core compartment more quickly than to the peripheral tissues, leading to large core-to-periphery gradients. After decoupling the heat lung machine, internal redistribution of heat causes afterdrop: a decrease in temperature of the core. Afterdrop slows down the patient’s recuperation process. Therefore, more knowledge is needed about the impaired thermoregulatory system during anesthesia and the effect of different protocols on temperature distribution. This thesis focused on the development of a computer model that is able to describe heat transfer during anesthesia with the emphasis on cardiac surgery. The model that was developed consists of three parts: 1) a passive part, which gives a simplified description of the human geometry by means of a multi-segmental, multi-layered representation of the body, and that takes into account all passive heat transfer processes, 2) an active part that takes into account the thermoregulatory system as function of the amount of anesthesia and 3) submodels, through which it is possible to adjust the surgery and patient specific boundary conditions. Heat transfer in the passive part was modelled with help of the Pennes’ bioheat equation. This equation was solved using spatial and temporal discretization schemes. Boundary con168 Summary ditions were formulated to account for conductive, convective, radiative and respiratory heat losses. Specific submodels were designed to model the thermal influences of the heart lung machine, forced-air heaters, heating mattress and the heat loss through the wound. For the development of the thermoregulatory model, patient data was required. To that end, a clinical experiment was conducted. Two groups of aortic valve patients were studied: one group was rewarmed with and one group was rewarmed without using forced-air warmers. A significant reduction of afterdrop was observed in the group that was rewarmed with forced-air heating. The active model was derived combining a pharmacological model and the data of the aortic valve patients. The pharmacological model was used to calculate the propofol (the most often used anesthetic agent) concentration in the blood. Anesthetic drugs lower the threshold for vasoconstriction in linear proportion to increased plasma concentration. A relation was derived between the anesthesia concentration calculated with help of the pharmacological model and the vasoconstriction threshold found in the aortic valve patients. As a first approach, a stepwise response was used to model the gain and intensity of the vasoconstriction response. The model was validated by comparing temperatures predicted by the computer model to experimental data. A method was developed to refine the vasoconstriction relations of the thermoregulatory model. It was possible to determine the intensity of the centrally mediated sympathetic vasoconstrictor tone and the proportional distribution coefficients for vasoconstriction on different body parts. The method was used in a study protocol involving healthy volunteers for three body parts. In addition, detailed measurements were performed on volunteers to obtain proportionality values for the other body parts. The refined vasoconstriction model was added in the whole body thermal model. The complete model was validated against experimental data of healthy subjects and cardiac patients and showed in general good agreement. The validity of the model was tested for other types of surgery, i.e. orthopedic back surgery and deep hypothermic surgery with circulatory arrest. Finally, the model was used to study the effect of different temperature protocols like the use of forced-air heaters, increasing the environmental temperature, using heating mattresses or using a mild hypothermia protocol instead of a moderate hypothermia protocol. Overall, the model is able to predict temperature responses of healthy persons and patients undergoing surgery at temperatures between moderate hypothermia and normothermia, with skin temperatures ranging between 30 and 34oC. If the boundary conditions and initial conditions are accurately known, the model predicts core temperature within typically 0.5oC and skin temperature within typically 1oC.

[1]  Hank Lin,et al.  Increasing Mean Skin Temperature Linearly Reduces the Core‐ temperature Thresholds for Vasoconstriction and Shivering in Humans , 1995, Anesthesiology.

[2]  D. Sessler,et al.  Mild perioperative hypothermia. , 1997, The New England journal of medicine.

[3]  J. Tarbell,et al.  A note on wall shear stress in the aorta. , 1982, Journal of biomechanical engineering.

[4]  K. Westerterp,et al.  Cold-induced heat production preceding shivering , 2005, British Journal of Nutrition.

[5]  N. Ghaddar,et al.  A new transient bioheat model of the human body and its integration to clothing models , 2007 .

[6]  D. Sessler,et al.  Perioperative thermoregulation and temperature monitoring. , 2006, Anesthesiology clinics.

[7]  R. Shephard,et al.  Spectral analysis of heart rate variability during heat exposure and repeated exercise , 1997, European Journal of Applied Physiology and Occupational Physiology.

[8]  van Aa Anton Steenhoven,et al.  Seasonal changes in metabolic and temperature responses to cold air in humans , 2004, Physiology & Behavior.

[9]  A. Gagge,et al.  Rational temperature indices of man's thermal environment and their use with a 2-node model of his temperature regulation. , 1973, Federation proceedings.

[10]  R. Fournier Basic Transport Phenomena In Biomedical Engineering , 1998 .

[11]  J. Kastner,et al.  Efficacy of Two Methods for Reducing Postbypass Afterdrop , 2000, Anesthesiology.

[12]  E. Wissler,et al.  Pennes' 1948 paper revisited. , 1998, Journal of applied physiology.

[13]  James D. Hardy,et al.  The technic of measuring radiation and convection , 1938 .

[14]  C. H. Wyndham,et al.  A physiological scheme and mathematical model of temperature regulation in man , 2004, Pflügers Archiv.

[15]  Judy L. Cezeaux,et al.  Accuracy of the inverse womersley method for the calculation of hemodynamic variables , 1997, Annals of Biomedical Engineering.

[16]  L Aarons,et al.  Physiologically based pharmacokinetic modelling: a sound mechanistic basis is needed. , 2005, British journal of clinical pharmacology.

[17]  R. Pearce,et al.  Determination of diffusion and partition coefficients of propofol in rat brain tissue: implications for studies of drug action in vitro. , 2004, British journal of anaesthesia.

[18]  D. Sessler,et al.  Thermoregulatory responses to hyperthermia during isoflurane anesthesia in humans. , 1993, Journal of applied physiology.

[19]  T. Moritani,et al.  Comparison of thermogenic sympathetic response to food intake between obese and non-obese young women. , 2001, Obesity research.

[20]  J. Michael Textbook of Medical Physiology , 2005 .

[21]  P. Höppe Indoor climate , 2005, Experientia.

[22]  K R Westerterp,et al.  A dual-respiration chamber system with automated calibration. , 1997, Journal of applied physiology.

[23]  R. Mann,et al.  Human Physiology , 1839, Nature.

[24]  D. Sessler,et al.  Perioperative heat balance. , 2000, Anesthesiology.

[25]  A. Seifalian,et al.  A mathematical analysis on the biological zero problem in laser Doppler flowmetry , 1998, IEEE Transactions on Biomedical Engineering.

[26]  P. O. Fanger,et al.  Thermal comfort: analysis and applications in environmental engineering, , 1972 .

[27]  V. Rajan,et al.  The relationship between local scalp skin temperature and cutaneous perfusion during scalp cooling , 2007, Physiological measurement.

[28]  Edward Arens,et al.  Indoor Environmental Quality ( IEQ ) Title A model of human physiology and comfort for assessing complex thermal environments , 2001 .

[29]  I. Jan,et al.  Adaptive processing bandwidth adjustment for laser Doppler flowmetry , 2004, Medical and Biological Engineering and Computing.

[30]  J D Hardy,et al.  Partitional calorimetric studies of man during exposures to thermal transients. , 1966, Journal of applied physiology.

[31]  Patricia J. Solomon,et al.  Application of therapeutic hypothermia in the intensive care unit , 2004, Intensive Care Medicine.

[32]  Hein A.M. Daanen Central and peripheral control of finger blood flow in the cold , 1997 .

[33]  R. Nossal,et al.  Model for laser Doppler measurements of blood flow in tissue. , 1981, Applied optics.

[34]  Jürgen Werner,et al.  The concept of regulation for human body temperature , 1980 .

[35]  D. Sessler,et al.  Skin-surface temperature gradients correlate with fingertip blood flow in humans. , 1990, Anesthesiology.

[36]  M. Cereda,et al.  Intraoperative Temperature Monitoring , 2004, International anesthesiology clinics.

[37]  K. Polderman,et al.  Application of therapeutic hypothermia in the intensive care unit , 2004, Intensive Care Medicine.

[38]  J. Pickard,et al.  Estimation of laser-Doppler flux biological zero using basilar artery flow velocity in the rabbit. , 1995, The American journal of physiology.

[39]  Jan A. J. Stolwijk,et al.  A mathematical model of physiological temperature regulation in man , 1971 .

[40]  C. Morrison,et al.  Waist circumference as a measure for indicating need for weight management , 1995, BMJ.

[41]  L. Sheiner,et al.  A semiparametric approach to physiological flow models , 1989, Journal of Pharmacokinetics and Biopharmaceutics.

[42]  Ola Eiken,et al.  Contribution of thermal and nonthermal factors to the regulation of body temperature in humans. , 2006, Journal of applied physiology.

[43]  F F de Mul,et al.  Principles and practice of the laser-Doppler perfusion technique. , 1999, Technology and health care : official journal of the European Society for Engineering and Medicine.

[44]  Y. Liu,et al.  Thermoregulatory reflexes and cutaneous active vasodilation during heat stress in hypertensive humans. , 1998, Journal of applied physiology.

[45]  J. Kastner,et al.  Tissue heat content and distribution during and after cardiopulmonary bypass at 17°C , 1999 .

[46]  T. K. Hunt,et al.  Oxygen as an antibiotic. A comparison of the effects of inspired oxygen concentration and antibiotic administration on in vivo bacterial clearance. , 1986, Archives of surgery.

[47]  D L Kellogg,et al.  In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. , 2006, Journal of applied physiology.

[48]  J. Durnin,et al.  Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 Years , 1974, British Journal of Nutrition.

[49]  S. Shafer,et al.  The Influence of Method of Administration and Covariates on the Pharmacokinetics of Propofol in Adult Volunteers , 1998, Anesthesiology.

[50]  D. Sessler,et al.  Deliberate Mild Hypothermia , 1995, Journal of neurosurgical anesthesiology.

[51]  T Moritani,et al.  Tone-entropy analysis on cardiac recovery after dynamic exercise. , 1997, Journal of applied physiology.

[52]  Wim H. M. Saris,et al.  Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis , 2008, PloS one.

[53]  K. Lomas,et al.  Computer prediction of human thermoregulatory and temperature responses to a wide range of environmental conditions , 2001, International journal of biometeorology.

[54]  S. Khuri,et al.  Hypothermia-induced reversible platelet dysfunction. , 1987, Annals of surgery.

[55]  T. Mort,et al.  The effects of forced-air warming on postbypass central and skin temperatures and shivering activity. , 1996, Journal of clinical anesthesia.

[56]  Barbara Kabon,et al.  Effects of a Circulating-water Garment and Forced-air Warming on Body Heat Content and Core Temperature , 2004, Anesthesiology.

[57]  Hein A.M. Daanen,et al.  Evaluation of wireless determination of skin temperature using iButtons , 2006, Physiology & Behavior.

[58]  C. H. Wyndham,et al.  Comparison of weighting formulas for calculating mean skin temperature. , 1969, Journal of applied physiology.

[59]  N M W Severens,et al.  Understanding post-operative temperature drop in cardiac surgery: a mathematical model. , 2008, Mathematical medicine and biology : a journal of the IMA.

[60]  A M Sessler,et al.  Leg Heat Content Continues to Decrease during the Core Temperature Plateau in Humans Anesthetized with Isoflurane , 1993, Anesthesiology.

[61]  U Braun,et al.  Perioperative thermal insulation: minimal clinically important differences? , 2004, British journal of anaesthesia.

[62]  Christian F. Bulcao,et al.  Relative contribution of core and cutaneous temperatures to thermal comfort and autonomic responses in humans. , 1999, Journal of applied physiology.

[63]  S Tsangaris,et al.  The inverse Womersley problem for pulsatile flow in straight rigid tubes. , 1988, Journal of biomechanics.

[64]  A J H Frijns,et al.  A model to predict patient temperature during cardiac surgery , 2007, Physics in medicine and biology.

[65]  Eugene H. Wissler,et al.  A quantitative assessment of skin blood flow in humans , 2008, European Journal of Applied Physiology.

[66]  Jintu Fan,et al.  A transient thermal model of the human body–clothing–environment system , 2008 .

[67]  D. Cook,et al.  Changing temperature management for cardiopulmonary bypass. , 1999, Anesthesia and Analgesia.

[68]  J. Y. Kim,et al.  The effect of skin surface warming during anesthesia preparation on preventing redistribution hypothermia in the early operative period of off-pump coronary artery bypass surgery. , 2006, European Journal of Cardio-Thoracic Surgery.

[69]  G Ward,et al.  A critical review of laser Doppler flowmetry. , 1990, Journal of medical engineering & technology.

[70]  Arjan J. H. Frijns,et al.  Validation of an individualised model of human thermoregulation for predicting responses to cold air , 2007, International journal of biometeorology.

[71]  D. Sessler,et al.  Desflurane Reduces the Gain of Thermoregulatory Arteriovenous Shunt Vasoconstriction in Humans , 1995, Anesthesiology.

[72]  Fem Francis-Paul Janssen Modelling physiological and biochemical aspects of scalp cooling , 2007 .

[73]  S Senn,et al.  Analysis of serial measurements in medical research. , 1990, BMJ.

[74]  J. Schefold,et al.  Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls , 2008, Critical care.

[75]  E. Stinson,et al.  Prosthetic replacement of the aortic arch. , 1975, The Journal of thoracic and cardiovascular surgery.

[76]  K. Cooper Some historical perspectives on thermoregulation. , 2002, Journal of applied physiology.

[77]  D. Sessler,et al.  Heat Balance and Distribution during the Core-Temperature Plateau in Anesthetized Humans , 1995, Anesthesiology.

[78]  M. Heymann,et al.  Distribution of systemic blood flow during cardiopulmonary bypass. , 1973, Journal of applied physiology.

[79]  K. Miki,et al.  Evaluation of mean skin temperature formulas by infrared thermography , 1997, International journal of biometeorology.

[80]  A A Van Steenhoven,et al.  Modelling of temperature and perfusion during scalp cooling , 2005, Physics in medicine and biology.

[81]  H. H. Pennes Analysis of tissue and arterial blood temperatures in the resting human forearm. , 1948, Journal of applied physiology.

[82]  M. Ozaki,et al.  I.m. midazolam as premedication produces a concentration-dependent decrease in core temperature in male volunteers. , 1997, British journal of anaesthesia.

[83]  Ulrich Braun,et al.  Conductive Heat Exchange with a Gel-Coated Circulating Water Mattress , 2004, Anesthesia and analgesia.

[84]  G. Hellige,et al.  Efficacy of postoperative rewarming after cardiac surgery. , 2004, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia.

[85]  M. Licker,et al.  Benefits of intraoperative skin surface warming in cardiac surgical patients. , 1998, British journal of anaesthesia.

[86]  J. Davis Organ Physiology Structure and Function of the Nervous System , 1977 .

[87]  J. Werner,et al.  A dynamic model of the human/clothing/environment-system. , 1997, Applied human science : journal of physiological anthropology.

[88]  M. Ozaki,et al.  Heat Flow and Distribution during Induction of General Anesthesia , 1994, Anesthesiology.

[89]  D. Delpy,et al.  Translational and Brownian motion in laser-Doppler flowmetry of large tissue volumes , 2004, Physics in medicine and biology.

[90]  D. A. Mcdonald,et al.  The relation of pulsatile pressure to flow in arteries , 1955, The Journal of physiology.

[91]  J Lagendijk,et al.  A description of discrete vessel segments in thermal modelling of tissues. , 1996, Physics in medicine and biology.

[92]  D. Sessler Perianesthetic thermoregulation and heat balance in humans , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[93]  Jan J W Lagendijk,et al.  Numerical Modeling of Temperature Distributions within the Neonatal Head , 2000, Pediatric Research.

[94]  J S Beck,et al.  Biological zero in laser Doppler measurements in normal, ischaemic and inflamed human skin. , 1993, International journal of microcirculation, clinical and experimental.

[95]  K. Lomas,et al.  A computer model of human thermoregulation for a wide range of environmental conditions: the passive system. , 1999, Journal of applied physiology.

[96]  D. Sessler,et al.  Tissue heat content and distribution during and after cardiopulmonary bypass at 31 degrees C and 27 degrees C. , 1998, Anesthesiology.

[97]  M Cabanac,et al.  Temperature regulation. , 1975, Annual review of physiology.

[98]  Steve W. Radons,et al.  Finite-element simulation of cooling of realistic 3-D human head and neck. , 2003, Journal of biomechanical engineering.

[99]  J. A. J. Stolwijk,et al.  Temperature regulation in man — A theoretical study , 1966, Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere.

[100]  A. Bjorksten,et al.  Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds , 1995, Anesthesiology.

[101]  Byron W. Jones Capabilities and limitations of thermal models for use in thermal comfort standards , 2002 .

[102]  Bas A J M de Mol,et al.  Effect of forced-air heaters on perfusion and temperature distribution during and after open-heart surgery. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[103]  C F Roe,et al.  Effect of bowel exposure on body temperature during surgical operations. , 1971, American journal of surgery.

[104]  W. Smith The Integrative Action of the Nervous System , 1907, Nature.

[105]  J. M. Coulson,et al.  Heat Transfer , 2018, Finite Element Method for Solids and Structures.

[106]  D. DuBois,et al.  A formula to estimate the approximate surface area if height and weight be known , 1989 .

[107]  M. M. Helland Organ Physiology: Structure and Function of the Nervous System , 1973 .

[108]  A. Shore,et al.  The biological zero signal in laser doppler fluximetry – origins and practical implications , 1999, Pflügers Archiv.

[109]  Makoto Ozaki,et al.  Rate and Gender Dependence of the Sweating, Vasoconstriction, and Shivering Thresholds in Humans , 1994, Anesthesiology.

[110]  A. Kurz,et al.  Thermal management of the patient: where does the patient lose and/or gain temperature? , 2005, Current opinion in anaesthesiology.

[111]  Andrea Kurz,et al.  Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds , 1995, Anesthesiology.

[112]  R. Thauer,et al.  [Physiology of heat regulation]. , 1955, Acta neurovegetativa.

[113]  The mathematical modelling of cooling and rewarming patients during cardiac surgery , 2006 .

[114]  R N Upton,et al.  A physiological model of induction of anaesthesia with propofol in sheep. 2. Model analysis and implications for dose requirements. , 1997, British journal of anaesthesia.

[115]  Benjamin S. Abella,et al.  Therapeutic hypothermia utilization among physicians after resuscitation from cardiac arrest* , 2006, Critical care medicine.

[116]  E. Sim,et al.  Deep hypothermic circulatory arrest in adults undergoing aortic surgery: local experience. , 2004, Annals of the Academy of Medicine, Singapore.

[117]  David G Levitt,et al.  Human physiologically based pharmacokinetic model for propofol , 2005, BMC anesthesiology.

[118]  Maciej Stańczyk,et al.  Discrete vessel heat transfer in perfused tissue—model comparison , 2007, Physics in medicine and biology.

[119]  R N Upton,et al.  A physiological model of induction of anaesthesia with propofol in sheep. 1. Structure and estimation of variables. , 1997, British journal of anaesthesia.