Research of resuscitation effects to organ functions in brain - Dead potential donors

havingexmination of the organ functions. Patients were not diagnosed with brain death according to Vietnamese law standards. Patients werenot treated correctly according to the regiment. 2.2. Methods 2.2.1. Design of study: Prospective, description, comparison before - after study (intervention of goal resuscitation). 2.2.2. Sample size: applying the sample size formula to the before- after studies. N = 47. 2.2.3. Drugs and facilities. - Drugs: infusion liquids, blood products, cathecolamine, endocrine. - Facilities: Monitoring, ventilator, blood-air test, PiCCO monitoring. 2.2.4. The content of Research. 2.2.4.1. The stages of research: T0: Background time (1st clinical 7 diagnosis of brain death); T1: After 12 hours: 3rd brain dead diagnose brain death 3 times (determined - conclusions); T2: After 24 hours of resuscitation of brain death (organ resuscitation); T3: After 36 hours of diagnosis and resuscitation of brain death; T4: After 48 hours of diagnosis and resuscitation of brain; Tm: Time before harvesting organs. 2.2.4.2. Criterias for evaluating a. General characteristics of patients Criteria for evaluating general characteristics of patients: - Anthropometric characteristics of the brain dead potential donors. + Causes of brain death, brain damage. +The need for using inotrops, vasopressine in the whole process. + Patient outcome after brain-dead resuscitation. b. Study of clinica l and laboratory characteristics in brain dead potential donors: We recorded the number of patients at the time T0 had the following clinical and laboratory indicators: The incidence of organ dysfunction in 47 potential brain deaths; Functions of cardiovascular; respiratory; kidney; liver and hematology; Fluid - endocrine and body temperature. SOFA: Total SOFA, individual SOFA, number of patients with multiple organ failure. c. Evaluate the effects of resuscitation measures on the functions of some organ in brain-dead potential donors. - Results of hormone replacement therapy: The rate of increased/decreased T3, T4, TSH, cortisol before and after treatment. - We recorded the number of patients at different times (T0, T1, T2, T3, T4, Tm) with the following changes in indicators: +The demands of cathecolamine; the demands for the kind of cathecolamine/ each patient; cathecolamine dose (Noradrenaline, Adrenaline, Dobutamine, Dopamine). 8 +The changes of basic hemodynamic through heart rate, MAP, CVP; the number of patients with decreased MAP< 70 mmHg, hypothermia ≤ 350C and diabetes insipidus. + The changes of SOFA scores; of lactat; of prothrombin rate; of plate let number. + The changes of respiratory and acidosis through parameters PaCO2, PaO2, PaO2 / FiO2; The changes of hepatic functions through blood glucose parameters, SGOT, SGPT, direct bilirubin; The changes of renal functions through blood ure, blood creatinine, urine output and dopamine dose. + Resuscitation results according to the target "rule 100", target "rule 100 *" amended through parameters maxBP, Hb, PaO2, urine output, Number of eligible patients. + Evolution of PiCCo invasive hemodynamic parameters through parameters CI, SVRI, GEDI and ELWI; Resuscitation results according to PiCCo instructions: CI ≥ 3 ml/min/m2 , GEDI ≥ 680 ml/m2, ELWI ≤ 10%, the number of patients meeting the criteria of 3 PiCCo parameters. - We record the number of patients after treatment by destination with the following indicators: + Cardiac arrest group vs or organ donation outcome in patients. + Number of organs eligible for transplant after resuscitation of 47 patients with brain death; number of organs eligible for transplant among resuscitated patients; organ transplantation results from a group of 47 patients with brain death considering organ donation; Transplant rate from 47 patients with brain death. + The percentage of organ transplants from 25 organ donors; Average number of days hospitalized after a transplant. 2.2.5. Method to proceed. 2.2.3.1. Step 1: Receive head trauma patients and install monitoring. 9 2.2.3.2.Step2: Thyroid hormone (T3,T4,TSH), Troponin T, cortisol; SVO2/SCVO2, blood-gas test, blood cell test, biochemistry test, coagulation test, urine test, SOFA score every 12 hours. 2.2.3.3. Step 3: Intensive resuscitation Table 2.1. The targets of resuscitation. Resuscitation measures. Targets Law 100* Systolic blood pressure ≥ 100, Urine output ≥ 100 ml/hour, PaO2 ≥ 100 mmHg, Hb ≥ 80 g/L PiCCo hemodynamic regimen CI ≥ 3 ml/min/ m2 GEDI ≥ 680 ml/m2 ELWI ≤ 10 %. Lung protected ventilation Donation: PaO2/FiO2> 300; FiO2 ≤ 0.5. No donation: PaO2>70 mmHg; SaO2> 88%. Hormone replacement therapy Levothyrox (belthyro x) 2,5 mcg/kg/24h Methylpresnisolon 15 mg/kg IV Maintain blood glucose 4-9 mmol/l. Treatment of diabetes mellitus Maintain Na + ≤ 155 mmol/L Maintain the volume of urine 1-2 ml/kg/hour Maintain body temperature 36 - 37 05 2.2.6. Criteria and definitions used in research. 2.2.7. Data analysis: SPSS 16.0 for Window. 2.2.8. Ethics in research. The research is a branch in the State-level project, which is approved by the Vietnam-Germany Professional and Ethical Council as well as by the Ministry of Science and Technology. In the process of implementing the research, we strictly adhere to the law on organ transplants of the National Assembly, regulations of the Ministry of Health. Resuscitation process has been approved by Vietduc Hospital. 10 CHAPTER 3 - RESULTS 3.1. General characteristics 3.1. General characteristics of research patients. 3.1.1. Anthropometric characteristics. Table 3.1. Age characteristics of brain death patients in the study. Comments: The average age is 32.91 ± 12.08 years old. Chart 3.1. Gender distribution of patients in the study. Comments: men account for 85.1% and females account for 14.9%. Table 3.2. Characteristics of weight and BMI of patients in the study. Comments: Average weight and BMI are suitable for VNese people. 3.1.2. Characteristics of injuries in brain-dead patients in the study. Table 3.3. Characteristics of cranial injuries of patients in the study. Comments: 17% of multiple injuries, 83% of head trauma alone. Intracranial hematoma, brain suppression, subarachnoid hemorrhage accounted for 76.6%. 3.1.3. Characteristics of cathecolamins use during resuscitation Table 3.4. Demands for cathecolamins in whole resuscitation process. Comments: The number of patients are treated noradrenalin accounted for the highest of 95.7%. 3.1.4. The outcome of the patients in the study. Chart 3.2. The patient's outcome after resuscitation. Comments: 100% death (46.8% biological death and 53.2% organ donation after brain death). 3.2. Clinical and laboratory characteristics in brain-dead potential donors. 3.2.1. Characteristics of complications and disorders after brain death. Table 3.5. Monitor body’s f luid - temperature status. Status Non diabetes ( X ±SD) Diabetes ( X ±SD) p 11 (n)/ (%) 14 (29,8% ) 33 (70,2% ) Body temperature (0C) 36,41 ± 1,31 36,10 ± 1,58 0,60 Urine output (ml/kg/giờ) 0,14 ± 0,11 0,55 ± 0,38 <0,001 Na+/plasma (mmol/l) 148,21 ± 13,04 152,36 ± 14,92 0,35 BOP (mosmol/kg) 300,78 ± 24,99 337,05 ± 20,07 <0,001 Comments: The average of urine output and blood osmolarity pressure in group with diabetes is significantly higher than the other. Table 3.6. The incidences of cardiac and pulmonary function index disorders before organ resuscitations. Organ Data Unit Criteria No.(n) Ratio(% ) Heart MAP mmHg < 70 10 21,3 CI l/min/m2 < 3 >5 23 2 48,9 4,3 GEDI ml/m2 < 680 > 800 47 0 100 0 SVRI dynes/cm5/m2 < 1970 > 2390 24 15 51,1 31,9 Lung PaO2/FiO2 < 300 16 33 PaCO2 mmHg < 35 > 45 29 2 61,7 4,3 pH < 7,25 > 7,45 0 31 0 66,0 ELWI ml/kg > 10 10 21,3 AOP pink foa m intubation 4 8,5 Comments: 21.3% of patients havehypotension <70 mmHg, 33% of patients had PaO2/FiO2 reduction <300 and 21.3% of patients have ELWI> 10. Table 3.7. The incidences of renal, hepatic and hematological function disorders before organ resuscitations. Organ Data Unit Criteria No.(n) Ratio (%) Kidney Oliguria Diabetes inspidusis ml/kg/h ml/kg/h < 0,5 > 4 0 33 0 70,2 Creatinine/plasma mmol/ l > 110 8 17,1 12 Natri plasma mmol/ l > 155 20 42,6 Kali plasma mmol/ l < 3,5 22 46,8 Liver SGPT UI > 2 lần 4 8,5 Glucose plasma mmol/ l >10 13 27,7 Bilirubin total µmol/ l > 20 8 17,1 Hematology Platelet No. G/l < 150 24 51,1 Prothrombine % < 60 17 36,2 Hemoglobine g/dl > 10 47 100,0 Comments: diabetes inspidusis 70.2%; 17.1% of liver dysfunction and 17.1% of renal dysfunction; 51.1% of decreased platelets <150 G/l; Table 3.8. Results of some cardiac function indicators in the resuscitation of brain death. Comments: Average EF = 63.09 ± 6.77%. Table 3.9. Results of screening ultrasound of livers and kidneys in resuscitation of brain death. Comments:abnormality of structure and image founded in 4 cases. Table 3.10. Hormone concentrationsof brain-dead potential donor patients before hormone therapies. Comments: before hormone therapies, decreased T3 is 91.5%, decreased cortisol is 27.6%. 3.2.2. The incidence of organ dysfunctions according to the SOFA score right before organ resuscitation. Table 3.11. The incidences of organ dysfunctions according to SOFA scorebefore organ resuscitation. Comments: Cardiovascular system: 83% of patients have SOFA 3 and 8.5% of patients have SOFA 4. 4.3% lungs with SOFA 3. 4.3% of patients has kidney with SOFA 2. Liver: 4.3% patients have SOFA2. hematologica l disorder: 4.3% patients have SOFA 3. 3.3. Evaluate the effects of resuscitation measures on the function of some organ in brain-dead potential donors 3.3.1. Results on hormone replacement therapy 13 Chart 3.3. The rate of increased/decreased T3 before and after treatment. Comments: After hormone therapies, the number of patients with decreased T3 is 44.7% (21/47). Chart 3.4. The rate of increased/decreased T4 before and after treatment. Comments: After hormone therapies, the number of patients with decreased T3 is 40.4% (19/47). Chart 3.5. The rate of increased/decreased TSH before and after treatment. Comments: After hormone therapies, the number of patients with normal TSH is 72.3% (34/47). Chart 3.6. The rate of increased/decreased cortisol before and after treatment. Comments: After hormone therapies, the number of patients with decreased cortisol is 8.5% (4/47). 3.3.2. The results of resuscitation for brain death stages after 12, 24, 36, 48 hours. Table 3.12. The demands of cathecolamine on each stage of organ resuscitation. Comments: the rate of noradrenaline using is very high all the stages, 100% in T3. Table 3.13. The demands for the kind of cathecolamine/ each patientin every resuscitation stages. Comments: using 1 kind of cathecolamine is highest (66%) at T0; using 2 kind of cathecolamine is highest (40%) at T4. Table 3.14. Cathecolamine dose in every resuscitation stages. Comments: The dose of noradrenaline significantly decreased at T1, T2, Tm. Table 3.15. The changes of basic hemodynamic after brain death diagnosis. Comments: MAP increased significantly every post- resuscitation stages. CVP increased significantly after T2. Table 3.16. The rates of complications in hypotension, hypothermia and diabetesin every stages. Comments: the rates of hypotension <70 14 mmHg gradually decreases after T1 (6.4%), T2 (2.7%), reincreases after T3, T4 (14.6% and 20%), the rates of hypothermia ≤ 350C and diabetes insipidus gradually decrease after resuscitation stages. Chart 3.7. The changes of SOFA scores in the brain-dead resuscitation stages. Comments: The averages of mean SOFA increase after every stages. Chart 3.8. The changes of lactat in brain-dead resuscitation stages. Comments: Blood lactate decreased significantly at T1, T2, Tm. Table 3.17. The changes of respiratory and acidosis during resuscitations. Comments: PaO2/FiO2- significantly reduced after T3. Chart 3.9. The changes of prothrombine rate in brain-dead resuscitation stages. Comments: The ratio of prothrombine has reduced significantly every stages. Chart 3.10. The changes of platelet during brain-dead resuscitation stages. Comments: Platelet reduces significantly during the resuscitations Table 3.18. The changes of hepatic functions during brain-dead resuscitation stages. Comments: The blood glucose of the patients significantly decreased in the T1, T3. Directed bilirubine increased significantly at T1, T2. Table 3.19. The changes of renal functions during brain-dead resuscitation stages. Comments: The output of urine decreases significantly in every stages. 3.3.3. Progress of archieving the organresuscitation targets inevery stages. Table 3.20. The results of resuscitation target according to Law 100. Comments: 60% of patients archieve the law 100 targets (highest) in Tm and 51.4% in T2. Table 3.21. The results of resuscitation target according to Law 100*. 15 Comments: 100% of patients archieve the law 100* targets (highest) in Tm and 86.5% in T2. Table 3.22. The changes of invasive hemodynamic parameters mesured by PiCCo after brain-dead diagnosis. Comments: GEDI significantly increased in T1, T2, T3, Tm. ELWI increased significantly at T3. Table 3.23. The results of resuscitation target according to PiCCo guidelines. Comments: After 24 hours (T2), 35.1% of patients archieve the PiCCo targets (highest). Table 3.24. The results of resuscitation folowing targets. Period No. of patients archieve PiCCO (1) n(%) No. of patients archieve 100 (2) n(%) No. of patients archieve 100* (3) n(%) No. of patients archieve (1)+(2) n(%) No. of patients archieve (1)+(3) n(%) T0 (n=47) 0 17 (36,2) 27 (57,4) 0 0 T1 (n=47) 6 (12,8) 18 (38,3) 37 (78,7) 1 (2,13) 5 (10,6) T2 (n=37) 13 (35,1) 19 (51,4) 32 (86,5) 9 (24,3) 13 (35,1) T3 (n=16) 2 (12,5) 6 (37,5) 9 (56,3) 1 (6,3) 2 (12,5) T4 (n=5) 0 0 0 0 0 Tm (n=25) 14 (56) 15 (60) 25 (100,0) 0 14 (56) Comments: The highest number of patients achieve all targets is in stage T2. 3.3.4. The results achieved the treatment goals of the donor group and cardiac arrest during each resuscitation period. Table 3.25. Cardiac arrest group vs donor group. Comments: The number of patients who achieved all targets at T2 and statistica lly different between groups of donors and cardiac arrest. 3.3.5. The number of organs eligible for transplant after resuscitation of 47 brain-dead potential donors. 16 Chart 3.11. The number of organs is suitable for transplantation among resuscitated patients. Comments: eligibility for kidney and heart donation are highest at T2 (54% and 48.6%); eligibility for liver and lung donation are highest at T4 (60% and 20%). 3.3.6. Outcomes of transplanted organs from 47 brain-dead potential donors. Chart 3.12. The proportion of new grafts from 47 brain-deadpatients. Comments: The number of grafted kidney is 50% (47/94) (highest), the grafted liver is 46.8% (22/47) and the grafted heart is 23.4% (11/47). Chart 3.13. The proportion of new grafts from 25 brain-dead donors. Comments: The number of grafted kidneys is 94% (47/50) (highest), the grafted livers is 88% (22/25) and the grafted hearts is 44% (11/25). Chart 3.14. The average numbers of hospitalization after transplantation. Comments: The longest hospitalized heart transplant patient, the shortest kidney transplant patient. CHAPTER4 - DISCUSSION 4.1. General characteristics of patients. 4.1.1. Characteristics of age, gender, weight. The average age was 32.91 ± 12.08 years old, lower than Weiss’s 17 study (54 ± 19.7). The rate of male is higher than of female (chart 3.1) and the majority of 40/47 (85.1%), female is 7/40 (14.9%). The average weight is 55.57 ± 6.30 kg and BMI is 18.62 ± 5.13 (Table 3.2) is suitable for the average size of Vietnam. 4.1.2. Causes and traits of brain death patients in the study. 100% of severe head trauma in which 83% of severe cranial injury, 17% suffered from multiple injuries (severe cranial injury mainly of brain hematoma, cerebral hemorrhage and haemorrhagic hemorrhage (up to 76.6%) (table 3.3). 4.2. Clinical and laboratory subclinical characteristics in brain dead potential donors. 4.2.1. Diabetes insipidus, electrolyte disturbances and body temperature. The rate of diabetes insipidus is 70.2%, urineoutput is 0.55 ml/kg/hour, and natriemia increase 152 mmol/l (Table 3.5). This rate in the study of Nguyen Quoc Kinh is 62.5%; Wood is 65%; Salim (2001) is 84%. The average temperature of diabetes insipidus group 36.10 ± 1.58 are different not significant for the group without diabetes insipidus, 36.41 ± 1.31 (p = 0.6) (Table 3.5). Hypernatremia > 155 are 42.6% in the study (Table 3.5). Cywinski has 20.4% hypernatremia > 155 mmol/l. 4.2.2. Hemodynamic and endocrine disorders. According to Salim, demands for cathecolamine is 97.1%, thrombocytopenia 53.6%, coagulopathy 55.1%, diabetes insipidus 46.4%, lactic acidosis 24.6%, renal failure 20.3%, and ARDS 13%. The results of our study have the rate of cathecolamine using (especially noradrenalin) is 95.7% (table 3.4), thrombocytopenia <150 G/L is 50.1% (table 3.7), coagulopathy (rate of prothombine time <60%) is 36.2% (Table 3.7), diabetes insipidus is 70.2% (Table 3.5), kidney failure is 17.1% (Table 3.7), respiratory dysfunction (PaO2/FiO2 < 300) is 33% (table 3.6). The period before brain-dead resuscitation, 91.5% (43/47) of our patients treated noradrenaline right from the beginning, higher than the results of the above authors, adrenaline was 12.8% (6/47), dobutamine is 10.6% (5/47) and dopamine is 10.6% (5/47) (table 3.12). Hoege (2007) and Schnuelle (2004) suggest that dopamine is the first cathecolamine due to effective vasoconstriction. The results of thyroid hormones in our study before treatment of 18 (nasal gastricsond) belthyrox corresponding to decreased T3, T4 by 43/47 (91.5%), 35/47 (74.5%); and normal/ increase TSH is 25/3 (total 59.6%) (table 3.10). But after treating belthyrox, decreased T3, T4 respectively to 21/47 (44.7%), 19/47 (40.4%); and the normal/ increase TSH level reached 37/47 (78.7%) (charts 3.3, 3.4, 3.5). In the study, normal and high cortisol before treatment was 42.6% and 29.8% (table 3.10). Kainz (2010), Barkin (2009) mentioned system inflammatory response syndrome (SIRS) in brain-dead. 4.2.3. Disorders of respiratory and acidosis We have 10/47 (21.3%) with a slight decrease of PaO2/FiO2 ratio in the range of 301-400, 4/47 patients (8.5%) had mild lung les ions PaO2/FiO2 (201-300) and 2/47 patients (4.3%) had severe lung lesions PaO2/FiO2 (<200) (ARDS) (table 3.11). Clinical acute pulmonary oedema (APO) with neurological cause was 8.5% (4/47) (table 3.6), compared with Smith (2004) and Salim (2006) ranging from 13-18%, also mainly neurological pulmonary edema. There were 21.3% of patients with extralung water index (ELWI> 10) (Table 3.6), which showed that the massively infusion liquids after brain-death due to prevent hypotension. About acidosis disorders, pH> 7.45 is quite high at 66% due to the high-volume ventilations of the before entering ICU (Table 3.6). 4.2.4. Disorder of blood glucose We had 27.7% (13/47) patients with hyperglycemia> 10 mmol / l (Table 3.7). Parekh (2011) studied over 40 recipients of kidney transplants from living kidney donors also found blood glucose> 8.8mmol/l related to impaired renal function after transplantation. 4.2.5. Organ dysfunction according to SOFA score In the pre-resuscitation period, the SOFA score corresponds to ≥ 2 points (SOFA score 2, 3 and 4) for cardiovasculars are 91.5%, respiratory 12.8%, livers 4.3%, kidneys 4.3 % and hematology (thrombocytopenia) 25.6% (table 3.11). The average SOFA score of the period T0 is 8.64 ± 2.27; the following stages corresponds to 9.30 ± 2.48 (T1), 9.51 ± 1.71 (T2), 10.44 ± 1.83 (T3), 11.4 ± 2.07 (T4) respectively, 9.38 ± 1.72 (Tm) and all stages having significantly increased SOFA (p <0.05) in the later stages compared to T0 (chart 3.7), but after 36 hours the average SOFA increased> 10. Nguyen Quoc Kinh (2012, 2013) found that the total SOFA score was statistically significant higher (p <0.05) in patients with cardiac arrest 19 compared to non arrest patients, among non arrest patients, it is better in group of eligible for organ donation compared to groupnon e ligible for organ donation (both are beating heart brain-dead donors). Essien (2017) finds that the current methods of definition organ failure or dysfunction have not yet fully predict the success of transplantations. 4.3. Evaluate the effects of resuscitation measures on the functions of some organ in brain-dead potential donors 4.3.1. The goals of resuscitation as guiding parameters of treatment for brain-dead potential donors. 4.3.1.1. Traditional monitoring parameters and prognosis of tissue hypoxia in brain dead potential donors. The average heart rate of our patients ranged from 105.3 to 108.14 times/min at T1 and T2, but trent to increase by 120.2 times/min at T4 stage but not significant. Average of MAP in groupremained at> 80 mmHg but increased significantly at T1 stage (89.2 ± 15.25) and Tm (101.67 ± 18.89) (p <0.05), CVP was maintained at 6-9 mmHg but statistically high after 24 hours was 8.51 ± 3.81 (p <0.05). The above results are had due to we try to optimize the volume of infusion (table 3.15). 4.3.1.2. The hemodynamic target of the brain-dead potential organ donors We have choosen the law 100* (modified) target (accept the patient's Hb at ≥ 8 g/dl), have 78.7% of our patients were eligible to donate organs after 12 hours and up to 86.5% of patients were eligible for organ donation after 24 hours (table 3.21) and reached 100% of patients when harversted organs. We resuscitated patients with brain death according to PiCCO guidelines and found that only 12.8% of patients met the criteria at the time of diagnosis after 12 hours, and then at 24 hours and 36 hours respectively. 35.1% and 12.5% of patients met the criteria for PiCCO target (Table 3.23). In the period of organ harvesting, there are 56% meeting a ll three PiCCo parameters. The patients who achieved both targets (PiCCo and 100) in our study were quite low at 2.13% after 12 hours, 24.3% after 24 hours and 2.13% after 36 hours; while achieving both goals (PiCCo and 100*), the rate of donation standard increased to 10.6% after 12 hours, 35.1% after 24 hours and 12.5% after 36 hours (table 3.24). At the time of donation, none of the patients achieved both PiCCo/100 20 targets and 56% achieved both PiCCo/100* targets. 4.3.1.3. The targets of infusion and blood transfusion. The main goal of body infusion control is to optimize all liquids to ensure circulation volume and cardiac flow suitably. During resuscitation, we kept the average CVP at 6.30 ± 3.97 at the beginning of resuscitation stage (T0) and the highest at 8.51 ± 3.81 at. 24 hours of resuscitation (table 3.15). 4.3.1.4. Hormone replacement therapy for brain-dead potential donors. - Vasopressin therapy: Plurad (2012) found that vasopressine in brain-dead donors was affected to the increasing of post-transplanted recovery rate. Our results showed that the incidence of diabetes inspitus gradually decreased to 42.6% after 12 hours and 27% after 24 hours and the time of organ harvesting was 16% (Table 3.16). - Corticosteroid therapy: we had 27.7% reduction in cortisol when diagnosed with brain death, the remaining 42.6% were normal and 29.8% increased cortisol immediately before resuscitation (table 3.10). Follette D (1998) and McElhinney (2001) found methylpresnisolon to be involved in improving lung quality of donors. We use high-dose corticosteroids (methylprednisolone 15mg/kg IV). Results of cortisol after treatment were 15.4%, 42.3% normal and 42.3% increased (chart 3.6). - Thyroid hormone replacement therapy: Howlett found that 81% of patients had decreased T3, 29% of patients had decreased T4, and 23% had normal TSH. After treatment, we had decreased T3 from 91.5% to 44% (chart 3.3); decreased T4 from 4