MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEATH HANOI MEDICAL UNIVERSITY ====== NGUYEN TUAN DAT ASSESSMENT OF THE BRAIN PROTECTION EFFECTS IN COMA PATIENTS AFTER CARDIAC ARREST BY THE METHOD OF H[.]
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEATH THE THESIS HAS BEEN COMPLETED AT HANOI MEDICAL UNIVERSITY HANOI MEDICAL UNIVERSITY ====== Academic Supervisors: Assoc Prof PhD NGUYEN VAN CHI Assoc Prof PhD HA TRAN HUNG NGUYEN TUAN DAT ASSESSMENT OF THE BRAIN PROTECTION EFFECTS IN COMA PATIENTS AFTER CARDIAC ARREST BY THE METHOD OF HYPOTHERMIA TREATMENT Reviewer 1: Reviewer 2: Reviewer 3: Specialism: Emergency and Clinical Toxicology Code number: 9720103 The thesis will be present in front of board of university examiner and reviewer lever at… on ….2022 SUMMARY OF MEDICAL DOCTORAL THESIS HA NOI - 2022 This thesis can be found at: - National Library: National Medical Informatics Library Library of Hanoi Medical University THE LIST OF WORKS HAS PUBLISHED AND RELATED TO THE THESIS Nguyen Tuan Dat, Nguyen Van Chi (2016), “Result of treatment in applying targeted temperature management of 33°C in patients who had been resusciated after cardiac arrest” Vietnam Medicine Journal, 449 (02) 12/2016, p 23 – 27 Nguyen Tuan Dat, Nguyen Van Chi (2016), “Evaluate the alteration in coagulation induced by applying targeted temperature management of 33°C in patients who were unconscious following cardiac arrest” Vietnam Medicine Journal, 450 (02) 1/2017, p 59-62 Nguyen Tuan Dat, Nguyen Van Chi, Ha Tran Hung, et al (2022), “Assessment of the treatment results and brain protection effects of the 33°C targeted hypothermia treatment in the treatment of coma patients after cardiac arrest” Vietnam Medicine Journal, 516 (01) 7/2022, p 63 – 67 Nguyen Tuan Dat, Nguyen Van Chi, Ha Tran Hung, et al (2022), “Assessment of some complications of the 33°C targeted hypothermia treatment in the treatment of coma patients after cardiac arrest” Vietnam Medicine Journal, 516 (01) 7/2022, p 152 – 155 INTRODUCTION Cardiac arrest is a sudden loss of effective myocardial contractility, common both in and out of the hospital, with a high mortality rate According to the report of the American Heart Association in 2016, there are about 350,000 out of hospital cardiac arrest and about 200,000 in-hospital cardiac arrest Despite advances in cardiopulmonary resuscitation, the outcome of patients with cardiac arrest remains poor with about 10% of patients surviving to hospital admission and about 5% having a good neurological recovery In the PAROS study in Vietnam, the hospital discharge rate was 14,1% After successful cardiopulmonary resuscitation, patients with return of spontaneous circulation (ROSC) mostly suffered brain damage due to ischemic - hypoxia during cardiac arrest and injury during reperfusion, which causes brain cell death, is the main cause of death and sequelae Hypothermia by a variety of mechanisms protects the brain from post-cardiac arrest injury Many studies on mild hypothermia (reducing core body temperature to 32°C - 34°C) conducted in comatose patients after cardiac arrest have improved neurological outcomes and increased survival rates, especially two groundbreaking studies: the HACA study in Europe and the Bernard study in Australia Several later clinical trials that compared target hypothermia of 33°C with target hypothermia of 36°C showed similar efficacy in mortality and neurological outcomes at the two target temperatures In the 2015 guidelines, the American Heart Association recommends the use of a target hypothermia of 32°C - 36°C for comatose patients after cardiac arrest at IB for outpatients with ventricular fibrillation, and an IC level with other arrhythmias and in-hospital cardiac arrest In 2020, the American Heart Association continues to raise the recommendation level to IB for all patients with cardiac arrest regardless of rhythm type Currently, in many countries around the world, hypothermia treatment for comatose patients after cardiac arrest is a standard and routine treatment modality In Vietnam, there is currently no research facility on this issue, so we conducted the study "ASSESSMENT OF THE BRAIN PROTECTION EFFECTS IN COMA PATIENTS AFTER CARDIAC ARREST BY THE METHOD OF HYPOTHERMIA TREATMENT" We selected the target temperature of 33°C in the study based on the physiological basis of better brain protection at lower temperature, not serious complications, as well as the evidence of research results HACA and Bernard's Research with two goals: Assessment of the treatment results and brain protection effects of the 33°C targeted hypothermia treatment in the treatment of coma patients after cardiac arrest Assessment of some complications of the 33°C targeted hypothermia treatment in the treatment of coma patients after cardiac arrest Thesis layout: The thesis consists of 135 pages with pages of introduction, 36 pages of literature review, 20 pages of subject and methods of the study, 30 pages of research results, 44 pages of discussion, pages of conclusions and page of recommendation New contributions of the thesis: The thesis has shown that the 33°C targeted hypothermia treatment is effective in improving the survival rate and the outcome of good neurological rehabilitation for comatose patients after out-ofhospital circulatory arrest The study also demonstrated that the 33°C target hypothermia treatment did not cause serious complications for the patient The successful application of the directed hypothermia technique to the resuscitation of patients after out-of-hospital cardiac arrest in Vietnam is an important contribution to the theory and practice of the Department of Emergency Medicine of Vietnam From this new contribution, the method of hypothermia treatment can be widely applied in emergency resuscitation units across the country CHAPTER LITERATURE REVIEW 1.1 Brain damage after cardiac arrest Cardiac arrest is the sudden loss of the heart's effective contractile function After successful cardiopulmonary resuscitation, patients with return of spontaneous circulation, the patient fell into the Post-cardiac arrest syndrome, which is a complex, multi-organ damage syndrome that is very severe The syndrome consists of the main lesions (1) Brain injury after cardiac arrest (2) Cardiac dysfunction after cardiac arrest (3) Systemic response due to ischemic injury, reperfusion causing activation of the immune system and coagulation, increases the risk of multiple organ failure, increases the risk of infection (4) The etiological damage to the cardiac arrest continues to progress Brain injury after cardiac arrest is a major cause of death and sequelae for patients, including ischemic injury (which occurs after cardiac arrest) and reperfusion injury (which occurs when the heart is beating again) During cardiac arrest, cerebral blood flow is stopped, oxygen supply is reduced, ATP production is stopped, leading to inactivation of energy dependent ion channels Because the Na+K+ATPase channel is deactivated, it cannot transport sodium (Na+) from the inside to the outside, depositing intracellular sodium (Na+) and causing cytotoxic edema ATP depletion, oxygen depletion leads to anaerobic metabolism, increased brain parenchymal lactate, intracellular acidosis, increases intracellular calcium (Ca2+) transfer through N-methyD-aspartate channels, thereby activating mitochondrial degrading enzyme, further reducing ATP A rapid increase in intracellular calcium concentration results in the release of large quantities of the neurotransmitter glutamate, further increasing the influx of calcium into the cell The increased intracellular calcium flux further activates phospholipase, increase synthesis NO, proteases, endonucleases, and oxidizing enzymes, causing the breakdown of cellular proteins and lipid membranes, leading to neuronal necrosis The accumulation of intracellular calcium causes impaired mitochondrial function leading to activation of apoptosis proteins in the chain reaction The pathological spiral becomes more and more complicated, forming a cascade of increasingly severe nerve damage that becomes irreversible if the ischemic time is prolonged Reperfusion injury is characterized by an imbalance in oxygen supply and use following cardiopulmonary resuscitation, leading to brain cell death, which occurs after the heart resumes During the reperfusion phase, the loss of membrane integrity leads to a marked increase in the concentration of glutamate, a neurotransmitter secreted by presynaptic neurons Glutamate activates a complex ion channel consisting of N-methyl-D-aspartate receptors and Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, increasing the permeability to calcium ions from the extracellular fluid into the cell flooding the cell with calcium ions, activating the mitochondrial respiratory chain to produce many free oxygen radicals Free oxygen radicals activate proteases, endonucleases, phospholipases, and oxidase enzymes, causing brain cell death 1.2 Mechanisms of brain protection when treating hypothermia Hypothermia treatment is a method using mechanical means to bring the core body temperature below the physiological temperature (< 36,5°C) Numerous animal studies have shown a protective effect on the brain when conducting hypothermia under command through multiple mechanisms - Decreased metabolism in the brain When the body temperature drops, it reduces the overall metabolism in the body, including the brain, reducing the need for oxygen and glucose Brain metabolism decreases by - 10% when body temperature decreases by 1°C A body temperature of 33°C reduces brain metabolism by up to 40%, which is especially significant in the context of the brain being deprived of oxygen and glucose - Prevents the programmed cell death pathway of brain cells After a period of ischemia and reperfusion, brain cells may necrosis, fully or partially recover, or die programmed Apoptotic death is thought to be caused by mitochondrial dysfunction, disturbances in cellular energy metabolism, and the release of multiple calcium-dependent proteolytic enzymes Hypothermia is thought to block the apoptosis pathway, protect brain cells by inhibiting the activation of calcium-dependent enzymes, prevent mitochondrial dysfunction, and reduce overload neurotransmitters that stimulate and regulate the concentration of ions in the cell - Prevents the cascade of nerve stimulation that is harmful to the brain Ischemic and reperfusion injury lead to a disruption of the delicate balance between calcium transport and absorption at the cellular level Numerous animal experiments have clearly demonstrated that the primary destructive process of the brain's harmful neuroexcitatory cascade (e.g calcium influx, accumulation of glutamate) can be prevented, disrupted, or mitigated by lowering body temperature Even a small decrease in temperature can significantly improve the homeostasis of ions, while fever can activate and stimulate destructive processes Several animal trials have suggested that toxic nerve excitability can be blocked or reversed if treatment is initiated in the very early stages of the excitatory cascade Other studies have reported slightly wider window times, ranging from 30 minutes to up to hours - Inhibits harmful inflammatory response Inflammatory and immune responses occur specifically during reperfusion and are accompanied by the production of free radicals This causes significant damage to brain cells Hypothermia inhibits the inflammatory response and release of proinflammatory substances caused by anemia Hypothermia also prevents or mitigates DNA damage, lipid peroxidation, and reperfusionrelated leukotriene production, and it reduces the production of nitric oxide, which is an important factor in increasing blood pressure postischemic brain injury - Reduced production of free oxygen radicals Another process of brain cell destruction is the release of free oxygen radicals after the ischemic - reperfusion injury Intermediates such as superoxide (O2-), Peroxynitrite (NO2-), Hydrogen peroxide (H2O2), and hydroxyl radicals (OH-) play an important role in determining whether injured cells will recover or die Free radicals can oxidize and damage many cellular components When the temperature is lowered, the number of free radicals generated is significantly reduced This allows cells to repair and repair themselves, rather than suffering permanent damage and dying - Reduce damage to the blood-brain barrier, reduce cerebral edema When ischemic - reperfusion injury can lead to significant disruption of the blood brain barrier, which in turn can cause cerebral edema Hypothermia significantly reduces blood brain barrier damage, and also reduces vascular permeability after ischemia - reperfusion, thereby reducing cerebral edema - Inhibit epileptic activity Nonconvulsive status epilepticus often occurs in patients after cardiac arrest Evidence suggests that brain damage is significantly increased when status epilepticus occurs during the acute phase of brain injury Hypothermia can inhibit epileptic activity 1.3 Clinical studies of hypothermia directed in comatose patients after cardiac arrest Two ground - breaking clinical trials (2002), demonstrated the effectiveness of hypothermia therapy in improving survival as well as good neurological outcomes in out-of-hospital cardiac arrest patients These are two randomized controlled studies (1) Study HACA is a multicenter study in Europe, including 274 patients with witnessing outof-hospital cardiac arrest, whose initial heart rate was a shockable rhythm, and due to etiology cardiovascular resources Patients in the intervention group were treated with a target hypothermia of 32 - 34°C by covering them with a cold blanket, maintaining the target temperature for 24 hours Study results showed that target hypothermia of 32 - 34°C improved survival as well as a good neurological outcome after hospital discharge with a good neurological outcome (55% vs 39%; RR 1.40 ; 95% CI 1.08 – 1.81); 6th month mortality (41% vs 55%; RR 0.74; 95% CI 0.58–0.95) (2) In the second study conducted in Australia, Bernard et al performed a randomized controlled study of 77 patients with out-of-hospital cardiac arrest whose initial heart rate was a shockable rhythm 43 patients treated for hypothermia with ice and covered with cold blankets maintained a target temperature of 33°C for 12 h Results were similar to the HACA study where 33°C target hypothermia improved survival at discharge with good neurological outcome (49% had good outcome vs 26% (RR = 1.85, 95% CI 0.97 – 3.49, P = 0.046) After multivariate analysis due to the difference between the groups, the odds ratio (OR) for good outcome in hypothermia group was up to 5.25 (95% CI: 1.47 –18.76, P = 0.011) Results of two randomized controlled trials show that mild hypothermia (32°C - 34°C) for 12-24 hours is effective in improving survival, improving neurologic outcomes for patients with comatose patient after out-of-hospital cardiac arrest, the initial heart rate is ventricular fibrillation/ventricular tachycardia Several later studies tested the effectiveness of hypothermia in command with a different temperature target Nielsen et al published the results of the TTM trial, which compared the effectiveness of target hypothermia treatment of 33°C versus 36°C This was a multicenter randomized clinical trial (36 centers in Europe and Australia) Study of 950 comatose patients after out-of-hospital cardiac arrest, including patients whose initial heart rate was shock or not, randomly divided into groups, one with hypothermia with a target temperature of 33°C, one group maintained at a target temperature of 36°C Use both surface and intravascular cooling, depending on the study site Outcomes at 6th month, all-cause mortality was similar among patients randomized at 33°C vs 36°C (50% vs 48%; p = 0.51) Mortality or survival with poor neurological function at 6th month was similar (54% vs 52%; p = 0.78) The FROST-I trial (2018) was a randomized controlled trial that studied 150 comatose patients after witnessed out-of-hospital cardiac arrest with an electrical shock baseline with three different target temperatures, respectively are 32°C, 33°C and 34°C The study results did not find a difference in the survival rate of hospital discharge with a good neurological outcome at 90th day at each target temperature However, trial with a rather small sample size To date, there have been no studies large enough to select the optimal target temperature The HYPERIO trial (2019) was a large randomized controlled trial evaluating the efficacy of hypothermia in patients with cardiac arrest with an initial non-shockable rhythm A study of 581 patients, including both out-of-hospital and in-hospital cardiac arrest, with baseline heart rate as non-shockable rhythm, randomly divided into groups with a target temperature of 33°C versus 37°C The proportion of patients with a good neurological outcome (CPC - 2) at 90th day was significantly higher in the 33°C target (10.2%) hypothermia group compared with 5.7% in the 37°C group ( 95% CI 0.1 – 8.9, P = 0.04) but there was no significant difference in overall mortality between groups (81.3% vs 83.2%) This is the first randomized controlled study to demonstrate the benefit of 33°C target hypothermia treatment for cardiac arrest with an initial nonshockable rhythm The 2015 Guidelines of the American Heart Association recommend the use of targeted hypothermia (32°C - 36°C) for comatose patients after cardiac arrest IB for out-of-hospital cardiac arrest due to ventricular fibrillation, and IC level with other arrhythmias and in-hospital cardiac arrest Based on the results of published studies on hypothermia, the American Heart Association's 2020 recommendation was increased for inhospital cardiac arrest and initial non-shockable rhythm Targeted temperature control (32°C - 36°C) is recommended for patients who lack of meaningful response to verbal commands after out-of-hospital, inhospital cardiac arrest with any rhythm, at level IB CHAPTER SUBJECT AND METHODS OF THE STUDY 2.1 Location of the study A9 Emergency Department - Bach Mai Hospital, from October 2015 to June 2021 2.2 Subject of the study 2.2.1 Criteria to select patients 1.2.1.1 Criteria to select patients in hypothermia group - Patients with out-of-hospital cardiac arrest due to ventricular fibrillation, asystole or pulseless electrical activity were successfully cardiopulmonary resuscitation, return of spontaneous circulation - The patient is still comatose (Glasgow score < 13 points) - The time from the return of spontaneous circulation to the onset of hypothermia is up to hours - Maintained blood pressure (systolic blood pressure ≥ 90 mmHg and mean arterial pressure ≥ 65 mmHg) - Age ≥ 18 2.2.1.2 Criteria to select patients in the retrospective control group - Patients meet the same selection criteria as the intervention group - The patient has never been treated with hypothermia How to select patients in the retrospective control group: look up all patients entering the A9 emergency department - Bach Mai Hospital from September 2015 and earlier, find all patients diagnosed with out-ofhospital cardiac arrest 2.2.2 Patient exclusion criteria - Coma before cardiac arrest due to other causes (sedation overdose, addiction, traumatic brain injury, brain stroke) - Use sedatives before entering the hospital - Severe infection or septic shock - Major surgery within 14 days - Patients with indications for intervention are at risk of interrupting the treatment of hypothermia command (surgical intervention ) - Clinically continuing heavy bleeding - Uncontrollable complex arrhythmia 10 - Zoll's Thermogard XP intravascular hypothermia - Intravascular Cooling Catheter ThermoGuard of ZOLL: In our study, types of catheters Cool line, Icy and Solex were used in our study 2.3.4 Treatment of controlled hypothermia according to the protocol (Figure 2.1) 2.3.5 Criteria for evaluating research by objective 2.3.5.1 Criteria for evaluating treatment results and brain protection effect - Main endpoint: o Survival at 30th day (short-term outcome) o Survival at 6th month (long-term outcome) - Secondary endpoint: assessment of neurological recovery o Change in Glasgow score before and after hypothermia treatment o CPC at 30th day (short term outcome) CPC at 6th month (longterm outcome) 2.3.5.2 Evaluation criteria for some complications Complications during hypothermia treatment - Chills, arrhythmias, blood potassium disorders, blood glucose disorders, coagulation disorder 11 Out-of-hospital cardiac arrest patient Endotracheal intubation – Mechanical ventilation Central venous catheter, arterial catheterization, gastric tube, bladder tube Treatment of hypotension: intravenous fluids, vasopressors (mean arterial blood pressure > 65 mmHg) ST-segment elevation myocardial infarction Coronary intervention before hypothermia non ST-segment elevation myocardial infarction Other causes Hypothermia first Hypothermia treatment Cooling Catheter; heat probe into the esophagus Control shivering Induction phase Cool as fast as possible with Maxpower mode Maintenance phase Duration: 24 hours Rewarming phase 0,25°C/ hours Normothermia phase maintain 37°C/ 24 hours Warm up now Uncontrolled arrhythmia/severe shock/bleed that is difficult to control Control blood sugar, electrolytes, arrhythmias, infections, convulsions Coagulation, biochemistry, infectious bilan, cardiac bilan at time To, T1, T2, T3, T4.Blood gases, glucose, Electrolytes at time T351, T¬33/2,T352 Echocardiogram on admission Daily chest X-ray Sputum culture, blood culture according to the procedure 1Discontinue muscle relaxants when reaching 36°C Discontinue sedation when reaching 37°C 12 CHAPTER RESULTS 3.1 General characteristic Table 3.1 Clinical characteristics of study patients Hypothermia Control Clinical characteristic group group p (n = 68) (n = 68) Age (mean ± SD) 43,9 ± 15,0 54,6 ± 16,0 0,0001 (range) (19 - 83) (22 - 86) Arrest witnessed - no (%) 66 (97,1%) 55 (80,9%) 0,003 Bystander performed cardiopulmonary 16 (23,5%) (5,9%) 0,004 resuscitation - no (%) Glasgow (median) (4 - 6) (4 - 6) 0,058 Temperature (°C) (mean ± SD) 37,5 ± 0,9 37,3 ± 0,8 0,419 Mean arterial blood pressure (mmHg) 92,5 ± 17,9 89,3 ± 19,9 0,166 Use of vasopressors - no (%) 57 (83,82%) 48 (70,59%) 0,066 3.2 Assessment of the results of 33°C target hypothermia treatment 3.2.1 Survival rate a Survival rate at the time of hospital discharge P = 0,003 Control group 33,8 Hypothermia group 66,2 58,8 0% 41,2 20% 40% 60% 80% 100% Survival Death Chart 3.1 Survival at hospital discharge in two patient groups Comment: Survival at discharge was significantly higher in the hypothermic group than in the control group (p = 0.003) 13 b Survival rate at 30th day P < 0,001 Control group 10,3 Hypothermia group 89,7 51,5 0% 48,5 20% 40% 60% 80% 100% Survival Death Chart 3.2 Survival rate at 30th day Comment: Survival at 30th day was significantly higher in the hypothermic treatment group than in the control group (p < 0.001) c Survival rate at 6th month P < 0,001 Control group 10,3 Hypothermia group 89,7 51,5 0% 20% Survival 48,5 40% 60% 80% 100% Death Chart 3.3 Survival rate at 6th month Comment: Survival at 6th month was significantly higher in the hypothermic treatment group than in the control group (p < 0.001) 14 d Survival analysis for year Chart 3.4 Survival time in year Comment: The Kaplan-Meier survival chart of the groups of patients showed that at any time in year, the survival rate of hypothermic patients was higher than that of the control group (p < 0.001) 3.2.2 Neurological rehabilitation results with 33°C target hypothermia treatment 3.2.2.1 Change in consciousness during treatment a Glasgow score at time of admission Table 3.2 Glasgow score at time of admission Glasgow (median) Hypothermia group (n = 68) Control group (n = 68) p Time Admission (4 - 6) (4 - 6) 0,058 Comment: At the time of admission, the patients were in a deep coma The median Glasgow score was similar in both groups This was advantageous in the study because the two groups were similar in terms of coma levels 15 b Glasgow score at 3rd day of treatment Table 3.3 Glasgow score on day of treatment Glasgow (median) Hypothermia group (n = 68) Control group (n = 68) p Time 3rd day (5 - 12) (3 - 7) P < 0,001 Comment: On the 3rd day of treatment (end of hypothermia treatment course), the hypothermia group survived 100% of the patients The control group survived 23 patients (33.8%) The hypothermic group had a significantly higher median Glasgow score than the control group c Change in Glasgow score before and after 33°C target hypothermia treatment Table 3.4 Glasgow score before and after hypothermia treatment Admission 3rd day Time P (n = 68) (n = 68) (4 - 6) (5 - 12) P < 0,001 Glasgow (median) Comment: The Glasgow score at the end of the 33°C target hypothermia treatment was significantly higher than the Glasgow score at the time of admission 3.2.2.2 Neurological rehabilitation results according to the CPC scale a Results of neurological rehabilitation of the two groups at 30th day P < 0,001 Control group 10.3 Hypothermia group 89.7 36.8 63.2 0% 20% 40% 60% 80% 100% CPC - CPC - Chart 3.5 Results of nerve recovery at 30th day 16 Comment: Good neurologic recovery (CPC 1-2) at 30th day was significantly higher in the hypothermic treatment group than in the control group b Results of neurological rehabilitation of the two groups at 6th month P < 0,001 Control group Hypotherm ia group 10,3 89,7 39,7 0% CPC - 60,3 50% 100% CPC - Chart 3.6 Results of neurological recovery at 6th month Comment: Good neurologic recovery (CPC 1-2) at 6th month was significantly higher in the hypothermic treatment group than in the control group 3.3 Complications during hypothermia treatment 3.3.1 Shivering 100% of patients in our study had shivering All are completely controlled with medication 3.3.2 Heart arrhythmia Table 3.5 Heart arrhythmia Heart arrhythmia Bradycardia < 40 Ventricular extrasystoles Ventricular fibrillation Ventricular tachycardia n (%) (10,3%) (2,9%) 0 17 Comment: Arrhythmias are uncommon, mainly Bradycardia, and ventricular extrasystoles 3.3.3 Blood potassium disorder Changes in blood potassium when 33°C target hypothermia treatment Table 3.6 Changes in blood potassium in the 33°C target hypothermia treatment Time means ± SD (mmol/L) Min – max P T0 T351 T1 T332 T2 T352 T3 3,7 ± 0,8 2,6 - 7,2 3,5 ± 0,7 2,5 – 6,2 3,7 ± 0,7 2,5 – 5,7 3,9 ± 0,8 2,4 – 5,7 3,8 ± 0,7 2,8 – 6,3 4,2 ± 0,8 2,9 – 6,8 4,5 ± 0,9 3,2 - 7,5 P = 0,0113 P > 0,05 P = 0,007 T4 4,4 ± 2,9 – 7,4 P > 0,05 Comment: - Hypokalemia during hypothermia Lowest at the time of reaching 35⁰C Serum potassium tends to stabilize at the maintenance phase - Blood potassium tends to increase in the warming phase, the highest increase at the end of the warming phase - Among patients with hypokalemia, the predominance of mild or moderate hypokalemia Only patient had severe hypokalemia 3.3.4 Increased blood sugar a Blood sugar at the time of admission Table 3.7 Blood sugar at the time of admission Glucose at admission (n = 68) Index Means ± SD (mmol/L) 14,4 ± 5,5 Hyperglycemia > 11,1 mmol/L (no, %) 49 (72,1%) Comment: Most patients have hyperglycemia on admission b Changes in blood sugar during 33°C target hypothermia treatment Table 3.8 Changes in blood sugar during 33°C target hypothermia treatment Time mean ± SD (mmol/L) P T0 T351 14,4 ± 5,5 14,6 ± 5,8 T1 16 ± 7,3 P = 0,002 T332 T2 T352 T3 T4 13,1 ± 6,3 8,9 ± 3,6 7,7 ± 3,2 7,6 ± 3,0 8,3 ± 3,5 P < 0,001 P = 0,34 18 Comment: - Hyperglycemia at the time of admission, blood sugar continues to rise during the hypothermia phase Increase is highest at the time the target temperature is reached - Blood sugar gradually decreases during the period of maintaining target temperature and stabilizes in the later stages 3.3.5 Coagulation disorder Table 3.9 Changes on coagulation in the study Time Platelet (G/L) P T0 T1 T2 T3 T4 (n = 68) (n = 68) (n = 63) (n = 63) (n = 57) 287,7 ± 72,2 263,5 ± 84,9 201,2 ± 68,3 175,6 ± 69,3 163,1 ± 61,1 (139 – 494) (113 – 588) (94 – 390) (68 – 439) (49 – 385) PT0T1 = 0,001; PT1T2 < 0,001; PT2T3 < 0,001; PT3T4 = 0,0023 Comment: Platelets tend to decrease gradually during the hypothermia treatment phase, the lowest decrease at the end of the phase of normalization of body temperature Most of the patients had platelets above 50 G/L, only patient had platelets as low as 49 G/L CHAPTER DISCUSSION 4.1 General characteristics of study patients The average age of the hypothermia group was 43.9 ± 15, the control group 54.6 ± 16, hypothermia group had a lower than the control group Compared to some studies, our patient had a lower average age, Phung Nam Lam was 52.2; of Dang Thanh Khan is 67.4; of Do Quoc Huy is 62, of Do Ngoc Son is 56.1; Vattanavanit V is 54.48; of Po-Yen Ko is 54.74 The rate of witnessed cardiac arrest in the intervention group was 97.1% higher than that in the control group of 80.9% (p = 0.003), similar to the study of HACA 98%, Bernard 94%, Vattanavanit V 91.3% The rate of witnessed cardiac arrest in our study was higher than in some previous studies in Vietnam such as Phung Nam Lam 75.8%, Dang Thanh Khan 73.1%, Do Ngoc Son 79.4% or Hoang Bui Hai 70.7%