Management of Sickle Cell Patients Undergoing Open Heart Surgery

Transcription

1 Management of Sickle Cell Patients Undergoing Open Heart Surgery Frank Edwin National Cardiothoracic Centre, Ghana Univ. of Health & Allied Sciences, Ghana

2 A Request from Leipzig, Germany Date: 5 th Nov, 2013 To: Liesl Zuhlke, Ped. Cardiologist UCT, SA Dear Madam, At the heart center in Leipzig, Germany we treat children with congenital heart diseases from Africa in cooperation with a charity organization. Since we have no experience with sickle cell disease and sickle cell trait in Germany, we would like to ask you about your protocol of perioperative management in patients with sickle cell hemoglobinopathy undergoing surgery with cardiopulmonary bypass. Does every patient with sickle cell disease or sickle cell trait receive exchange transfusion before surgery or during cardiopulmonary bypass? Do you use hypothermia during surgery? What would you recommend for patients with sickle cell trait? Dr. med. Nicole Pfeil Edwin F. NCS

3 Fwd: Request from UCT to Joburg Hi Jeff and Antoinette, Can you help with this query? We have not experienced this on a regular basis. Regards, Liesl Edwin F. NCS

4 Fwd: To Rob Kinsley in Sunninghill Dear Prof Kinsley, Do you have a protocol for managing patients with sickle cell anemia undergoing cardiopulmonary bypass and hypothermia? See from Liesl below. Regards, Antoinette. Edwin F. NCS

5 Fwd: To Accra Hi Frank, Can you help with this. I have no experience but wonder if you have encountered patients in West Africa? Regards, Rob Edwin F. NCS

6 Why The Concern with SCD and Open Heart Surgery? Edwin F. NCS

7 Periop. Complication Rate in SCD (Orthopedic Surgery) Vichinsky EP et al. Am J Hematol Nov;62(3): Overall serious complication rate: 67%. Most common: Excessive intraoperative blood loss (> 10% of blood volume). Sickle cell-related events (17%) Acute chest syndrome Vaso-occlusive crisis which occurred in 17% of cases. Transfusion complications 12% Increased risks of peri-operative mortality, and acute kidney injury. (Adjepong KO et al. Mediterr J Hematol Infect Dis. 2018; 10(1): e ) Higher risk procedures were associated with significantly higher rates of overall complications. Edwin F. NCS

8 Concerns: Open Heart Surgery Requirement for intra-op cardiopulmonary arrest Use of non-oxygenated cardioplegic solutions Aortic X-clamp --- intra-coronary sickling Low flow state; circ. arrest, hypoxia, acidosis Blood flow across un-physiologic surfaces Use of hypothermia for organ protection Profound surgical trauma Edwin F. NCS

9 Response to Concerns Evolution of practice guidelines under problematic circumstances Small case volumes in European and American centers: mostly case reports in Hb AS patients No controlled studies Epicenters of SCD were not performing OHS Suggestions of earlier workers evolved into guidelines and commandments. Edwin F. NCS

10 Current Recommended Guidelines and their Origins Edwin F. NCS

11 Coexistence of SCD and CHD With Open Heart Surgery in Two Pxs Harris LC et al. Pediatrics 1964; 33: In view of what is known of the pathogenesis of the manifestations of sickle cell disease, it seemed logical, therefore, to reduce the level of hemoglobin S by the administration of hemoglobin A blood detectable amounts of hemoglobin S virtually disappeared, and the possibility of complications arising from the sickling phenomenon was eliminated. Edwin F. NCS

12 Results The prevailing idea was If you replace Hb S with Hb A, you replace a SC patient with a Hb AA patient without risk of peri-op sickle cell related complications. Well, when they did so, the patients survived without sickle cell related complications, confirming the validity of the assumption! Perioperative exchange transfusion was born! More assumptions were added: avoid hypothermia, don t X-clamp the aorta, avoid cold crystalloid cardioplegia, and others. Edwin F. NCS

13 Full Precautionary Measures Sutton SW et al. Tex Heart Inst J 1999;26: Preop Ex. Tx (reduce Hb S to < 30%) Normothermia for CPB Platelet sequestration Continuous hemofiltration Warm, oxygenated cardioplegia solutions Beating heart op; avoid topical hypothermia But these were all based on logic, not evidence; because others broke all these rules and got the same results! Edwin F. NCS

14 Evidence from Previous Cases Métras D, Coulibaly OA, Ouattara K, Longechaud A, Millet P, Chauvet J. Open-heart surgery in sickle-cell haemoglobinopathies: report of 15 cases. Thorax. 1982; 37: Edwin F. NCS

15 Open-heart Surgery in Sickle-cell Hemoglobinopathies: Report of 15 Cases. Thorax. 1982; 37: Edwin F. NCS

16 Open-heart Surgery in Sickle-cell Hemoglobinopathies: Report of 15 Cases. Thorax. 1982; 37: Edwin F. NCS

17 Edwin F. NCS

18 Accra 1998 Frimpong-Boateng K, Amoah AG, Barwasser HM, Kallen C. Cardiopulmonary bypass in sickle cell anaemia without exchange transfusion. Eur J Cardiothorac Surg Nov;14(5): Frimpong-Boateng K, Aniteye E, Amoah AGB, Amuzu V, Konotey-Ahulu FID. Cardiopulmonary bypass surgery in sickle cell disease: an update. Ghana Med J, 2001, vol. 35 (pg ) Edwin F. NCS

19 ACS after AVR 59 yr old HbSS patient underwent AVR. Full precautionary measures. Hb S reduced to 20% Normothermic (37 ) CPB Warm blood cardioplegia Life-threatening acute chest syndrome POD 6. Murtuza B, Gupta P, Lall KS. The acute chest syndrome of sickle cell disease following aortic valve replacement, Interact CardioVasc Thorac Surg, 2009, vol. 9 (pg ) Edwin F. NCS

20 CPB Using Ex Tx in SCD/SCT 43 SCD & 4 SCT patients Study aim: Evaluate outcome of open heart surgery in patients with sickle cell hemoglobinopathy at our institution Notably study used no control data Ex Tx reduced HbS to 8.1 ± 2.6% CPB temperatures kept above 32 C. Early mortality rate 2.1% Stroke 4.3% Renal failure 4.3% Prolonged mech. Vent. 2.1%. Yousafzai SM, Ugurlucan M, Al Radhwan OA, Al Otaibi AL, Canver CC. Open heart surgery in patients with sickle cell hemoglobinopathy, Circulation, 2010, vol. 121 (pg ) Edwin F. NCS

21 Reconsider the Assumptions! The presence of supportive data can suggest a hypothesis is true. This was the case in the 60 s. Absence of confirmatory evidence does not necessarily disprove a theory; it only means the hypothesis is unproven. Contradictory evidence means that the theory must at least be revised, if not entirely rejected! Edwin F. NCS

22 What is the Best Available Evidence? What are our results? Edwin F. NCS

23 : Procedures on Hb S Pxs. HbAS VSD 6 MVR 5 ASD 5 AVR 2 TOF 3 HbSS VSD 3 MVR 2 ASD 1 DVR 1 HbSC VSD 1 MVR 1 ASD 2 TVRcst. 1 Edwin F. NCS

24 Management Strategy Elective patients should be in steady state Ensure adequate tissue perfusion Avoid dehydration Avoid hypotension Adequate oxygenation Avoid hypoxia Avoid hypoventilation Use hypothermia but Full re-warming after CPB Warm blankets post op if cold Warm transfusions post op Edwin F. NCS

25 Transfusion Triggers Hb between steady state and 10g/dl for Hb SS/SC Hb 10g/dl for HbAS Edwin F. NCS

26 CPB Protocol 1 Machine Prime: ml of Ringers Lactate 20-40ml of 8.4% NaHCO units heparin ± 450ml whole blood (anemia, < 35kg, <12 yrs) CPB HCT: 15-20% for HbSS/SC; 24-30% for HbAS Systemic hypothermia: 23.8 C 33.5 C Flow ml/kg/min Perfusion pressure 55 mmhg Edwin F. NCS

27 CPB Protocol 2 po 2 300mmHg ph in HbSS/SC; HbAS Cannulation aortic & bi-caval Cold crystalloid cardioplegia 30ml/kg for induction 15ml/kg q25 min +Topical cold saline Termination of CPB HCT of 24 30% for HbSS/SC; 30% for HbAS Re-warm to rectal temperature 36 C Edwin F. NCS

28 Study Design Retrospective analysis 1:1 Matched-pair case control methodology Inclusion Criteria Cases: All CPB; Hb AS, SS, SC pts. (Jan 1995 Jan 2014) Controls: Hb AA (surrogates for Ex Tx Hb S patients) Matching criteria Sex Identical Age ±5 yrs Weight ±5kg ( 12 yrs); ±10kg (>12 yrs) Procedure Identical or nearly identical Edwin F. NCS

29 Outcome Measures Primary Early mortality Measures of organ injury Painful VOC Acute Chest Syndrome Stroke Acute Kidney Injury Secondary Surrogates for hemolysis (hyperbilirubinemia, hemoglobinuria) Blood loss from mediastinal drains Red cell transfusion requirement Intensive care unit stay Hospital length of stay Edwin F. NCS

30 Results 33 (3.2%) sickle-cell pts. of 1,038 OHS pts. Sickle Cell Trait (HbAS) = 21 Sickle Cell Disease = 12 HbSS = 7 HbSC = 5 Age, sex, weight, and procedure-matched controls Edwin F. NCS

31 Matched-pair Data: HbAS HbAS HbAA P value Age (yrs) 15.8± ± Weight (kg) 38.7± ± Pre-op Hb (g/dl) 13.2± ± XCT (min) 58.5± ± CPBT (min) 100.6± ± CPB Temp ( ) 28.4± ± Edwin F. NCS

32 Matched-pair Data: HbSS HbSS HbAA P value Age (yrs) 13.6± ± Weight (kg) 36.6± ± Pre-op Hb (g/dl) 8.5± ±1.9 <0.01 XCT (min) 56.0± ± CPBT (min) 92.3± ± CPB Temp ( ) 27.9± ± Edwin F. NCS

33 Matched-pair Data: HbSC HbSC HbAA P value Age (yrs) 13.2± ± Weight (kg) 38.2± ± Pre-op Hb (g/dl) 11.0± ± XCT (min) 39.0± ± CPBT (min) 74.4± ± CPB Temp ( ) 30.4± ± Edwin F. NCS

34 Outcome Measures Primary outcomes No mortality No S-cell crises or S-cell related complication Secondary Outcomes No exx bilirubinemia, no hemoglobinuria Edwin F. NCS

35 Noteworthy Complications Chest infection 1 Reoperation for residual VSD 1 Nasal mucosal bleeding (assoc. gnathopathy) 2 Lesson: avoid nasal intubation when gnathopathy + Edwin F. NCS

36 Secondary Outcomes: HbAS HbAS HbAA P value Post-op H ge (ml) 739± ± Blood Tx/kg (ml/kg) 13.9± ± Inotropic Support (days) 2.2± ± ICU Stay (days) 4.3± ± Hospital Stay (days) 11.8± ± Edwin F. NCS

37 Secondary Outcomes: HbSS HbSC HbAA P value Post-op H ge (ml) 727± ± Blood Tx/kg (ml/kg) 30.0± ± Inotropic Support (days) 1.9± ± ICU Stay (days) 5.9± ± Hospital Stay (days) 15.3± ± Edwin F. NCS

38 Secondary Outcomes: HbSC HbSC HbAA P value Post-op H ge (ml) 493± ± Blood Tx/kg (ml/kg) 13.1± ± Inotropic Support (days) 1.6± ± ICU Stay (days) 3.2± ± Hospital Stay (days) 10.6± ± Edwin F. NCS

39 Essential Findings HbAS pts tolerate CPB with little alteration to std protocol Preoperatively, HbSS and HbSC patients were anemic. HbSS pts req. more blood transfusion than controls. Mortality or S-cell-related complications were not increased by avoiding Ex Tx. Hypothermia during CPB was tolerated without complications In-patient stay was similar for S-cell pts. and controls. Edwin F. NCS

40 Edwin F. NCS

41 16 More Post 2014 Hb SS (3) VSD Repair 2 DVR 1 Hb SC (1) VSD PDA Repair 1 Hb AS (12) VSD Repair 6 TOF Repair 4 DORV Repair 1 AVSD Repair 1 Edwin F. NCS

42 Conclusion ExΔ Tx is not essential in S-cell pts undergoing CPB. Tx needs for Hb SC & AS pts are similar to matched Hb AA controls. A simple Tx regimen to replace blood loss is safe in Hb SS pts. Use of systemic hypothermia during CPB does not increase S-cellrelated complications. Cold crystalloid cardioplegia and topical hypothermia provide safe myocardial protection without the need for more sophisticated measures. Edwin F. NCS