The Safety of a Conservative Fluid Strategy in Adults Hospitalised with Malaria

Transcription

1 The Safety of a Conservative Fluid Strategy in Adults Hospitalised with Malaria Ne Myo Aung, Myat Kaung, Tint Tint Kyi, Zaw Win Htet, Myat Phone Kyaw, Myo Min, Nicholas M Anstey, Mar Mar Kyi, Josh Hanson Myanmar-Menzies Collaboration Research Group

2 Case Scenario 1 WN, 18 yr old gentleman, admitted on Chief Complaint Fever with chills and rigor x 8 days Delirium x 1 day No urine output x 1 day Returned from Kyauk-phyu tsp, Rakhine Region, 1 month ago

3 Case Scenario 1 Physical examination GCS 15/15 Jaundice (+) Pallor (+) CVS, Resp NAD Liver 2cm No splenomegaly

4 Case Scenario 1 RDT malaria P.f (+)ve Blood for MP ( ) P.f (++) P.v (+) Blood for MP ( ) P.f (+) Hb WBC Plt Neut Lym Mono

5 Case Scenario 1 Urea Na K Cl HCO3 Cr T. Bil AST ALT ALP He was treated as severe malaria and discharged after cured.

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9 800 Intravascular volume (GEDI ml/m2) Hanson et al. Journal of Infectious Diseases 2012

10 Effect of acidosis and AKI on mortality in SEAQUAMAT Mortality % Base deficit <6 Base deficit 6 BUN <60 BUN 60 Dondorp et al. Lancet 2005

11 Renal Involvement in Severe Malaria (Insein General Hospital, ) Mar Mar Kyi, Myat Phone Kyaw, Myat Htut Nyunt, Tint Tint Kyi, Kyi May Htoo, Ne Myo Aung, Thinzar Cho Oo, Mi Mi Khine, Kyi Aye Thet

12 Renal Involvement in Severe Malaria Total number of patients 48 Creatinine cut off point for renal involvement 120 µml/l

13 Renal Involvement in Severe Malaria Results Malaria species 4, 8% P.v P.f 44, 92% Non of the P.v patients had renal involvement.

14 Renal Involvement in Severe Malaria Results All severe malaria cases 17, 35% Renal Involvement 31, 65% No renal involvement

15 Renal Involvement in Severe Malaria Results Expired cases 1, 17% Renal Involvement 5, 83% No renal involvement

16 Simple Clinical & Laboratory Parameters can Predict Prognosis

17 Coma Acidosis Malaria (CAM score), Bicarbonate based CAM score and RR based CAM score

18 Variable Normal 0 points Abnormal 1 point Very abnormal 2 points Bicarbonate 23 <23 but >15 15 GCS 15 >10 but <15 10 Variable Normal 0 points Abnormal 1 point Very abnormal 2 points Respiratory < rate GCS 15 >10 but <15 10 RCAM Score R Respiratory rate C Coma A Acidosis M Malaria RCAM<2: Positive predictive value for survival: 92%, PPV for survival to 72h: 99.7%

19 Dondorp et al ACTA Tropica 2004

20 Adjuvant therapy Heparin Prostacyclin Desferrioxamine N-acetylcysteine Pentoxifylline Dextran Urea High-dose steroids Acetylsalicylic acid Erythropoietin Mannitol Anti-tumour necrosis factor antibody Cyclosporin Dichloroacetate Adrenaline Hyperimmune serum Levamisole

21 No adjuvant therapy has ever been shown to improve survival So we need to improve our supportive care.

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23 Relative risk (95%) 1.59 ( )

24 Deterioration in acid-base status No meaningful improvement in renal function Increase in lung water Increase in peripheral oedema CCM 2013

25 Hanson et al. Critical Care Medicine 2013 Baseline ph Change in ph after 6h fluid loading

26 Baseline creatinine Change in creatinine after 24 hours fluid resuscitation

27 Lung water at baseline Change in lung water after 6 hours

28 = 5 died: the only deaths in the study

29 Malaria Guidelines Adjunctive treatment in severe malaria Management of Acute Renal Failure 1) Fluid Management 2) Nephrotoxic drugs should be avoided 3) Exclude dehydration 4) Carefully infuse isotonic saline until venous pressure reaches between 0 and 5 cmh₂0. 5) Peritoneal dialysis or haemodialysis if the patient remains oliguric after adequate rehydration and the blood urea and creatinine rise progressively.

30 Risks of more conservative fluid delivery Exacerbate Acute Kidney Injury Exacerbate lactic acidosis Exacerbate existing hypovolaemia with risk of hypotension

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32 The study Adults ( 16) admitted to Insein General Hospital or Hpa-an Hospital with malaria between April 15 and December Excluded: shock (SBP<80) Anuria Pulmonary oedema Adequate oral intake Hb < 7 and patient able to receive blood transfusion within 6 hours. Pregnancy

33 Protocol Patients received IV fluid administered at a maintenance rate more conservative than WHO guidelines (published after study began) Otherwise standard care as per National Myanmar Malaria Treatment Guidelines

34 How conservative? Based on rule for maintenance fluid Oh TH Anesthesiology 1980; 53(4): 351 Weight (kg) ml/hr Females 45.5 kg kg/cm for each cm > 152 cm. Males 50 kg kg/cm for each cm > 152 cm.

35 How conservative? Weight (kg) 4 6 Weight 8 10(kg) ml/hr ml/hr Initial fluid: Normal saline

36 Enrolment Baseline bloods collected Indwelling urinary catheter inserted Commence IV N.Saline at weight based rate MAP<60mmHg UO<0.5ml/kg/h MAP >60mmHg & UO>0.5ml/kg/h bolus of 5ml/kg bolus of 5ml/kg Continue IV fluids at the same rate MAP still <60mmHg after bolus Reassess at next hour mark Repeat bolus hourly if necessary MAP & UO OK IV fluids at the same rate Repeat 5ml/kg bolus If no response after 4 hours consider RRT When oral intake commences halve IV fluid rate. When adequate cease. MAP still <60mmHg after second bolus. Consider 1. Further fluid challenge 2. Empirical antibiotics 3. Inotropic support 4. Watchful observation if otherwise clinically well Bolus over 15 minutes

37 Endpoints Primary endpoint: Lactate clearance Secondary endpoints Incidence of AKI Incidence of pulmonary oedema Death

38 Results 51 patients met eligibility criteria 35 Plasmodium falciparum 17 Plasmodium vivax Using algorithm patients received a mean of 1.7ml of IV saline per kg/h in the first 6 hours. Some had an oral intake in addition leading to a mean of 2.6ml of total fluid per kg/h in the first 6 hours.

39 Results In the first 24 hours Mean 1.7ml/kg/h IV fluid Mean 2.5ml/kg/h of total fluid In the first 48 hours Mean 1.6ml/kg/h IV fluid Mean 2.5ml/kg/h of total fluid

40 Results With this conservative fluid strategy NO patient died NO patient developed acute kidney injury NO patient required RRT NO patient developed pulmonary oedema NO patient developed shock

41 Plasma lactate with rehydration Plasma lactate (mmol/l) hours 24 hours 48 hours Time after enrolment

42 Patients with elevated lactate on admission 4 3 Plasma lactate (mmol/l) hours 24 hours 48 hours Time after enrolment

43 Plasma creatinine with rehydration Plasma Creatinine (µmol/l) hours 24 hours 48 hours Time after enrolment

44 Patients with impaired renal function on admission Plasma Creatinine (µmol/l) hours 24 hours 48 hours Time after enrolment

45 Clinical findings t=0 t=24 t=48 GCS 14 (14-15) 15 (14-15) 15 (15 15) Temperature 39 ( ) 37.5 ( ) 37.2 ( ) MAP 82 (79-85) 83 (81-86) 84 (81-86) Pulse 96 (91-101) 87 (83-91) 83 (80-85) SaO2 97 (97-98) 98 (98-98) 98 (97-98) RR 31 (29-33) ) 21 (20-23)

46 Laboratory findings t=0 t=24 t=48 Sodium 136 ( ) 134 ( ) 139 ( ) Potassium 3.7 ( ) 3.5 ( ) 3.7 ( ) Chloride 103 ( ) 103 ( ) 104 ( ) Urea 6.4 ( ) 5.1 ( ) 4.7 ( ) Creatinine 115 (91 139) 105 (75-135) 96 (71-121) Glucose 6.6 ( ) 6.8 ( ) 6.2 ( ) ph 7.40 ( ) 7.40 ( ) 7.39 ( ) Bicarbonate 22.8 ( ) 23.4 ( ) 24.2 ( ) Lactate 1.98 ( ) 1.26 ( ) 1.10 ( ) Base deficit 2 (1-3) 1 (0-2) 1 (0-2) Haemoglobin 11.0 ( ) 10.2 ( ) 10.2 ( )

47 Mortality by RCAM in previous series

48 Mortality 2013: 7/20 (35%) with RCAM 2 This series 0/22 with RCAM 2

49 Other endpoints Lactate steady fall despite conservative fluid therapy Creatinine fell sequentially in all patients, none required RRT (fortunately) No pulmonary oedema, shock

50 Future Data need to be confirmed in a larger cohort or sicker patients However these data suggest that the fluid load recommended in current WHO consensus guidelines based only on expert opinion does not need to be so liberal. Studies are continuing.

51 What we need to consider Development of AKI is a major determinant of mortality in severe malaria. Creatinine cut off value of 265 needs to be evaluated. How much fluid is optimal in severe malaria?

52 References 1. Health in Myanmar, (2014) 2. Mar-Mar-Kyi, (2013): Challenges and Future perspectives in Severe Malaria Management 3. Myat-Kaung, Tint-Tint-Kyi, Ne-Myo-Aung et al., (2014): The prognostic utility of bedside assessment of adults hospitalized with malaria in Myanmar: a retrospective analysis 4. Myat-Phone-Kyaw, (2015): Heterogeneity, Complexity and Polymorphisms of Artemisinin Resistance Markers in Myanmar 5. National Malaria Control Programme, (2015): Guidelines For Malaria Diagnosis And Treatment In Myanmar 6. Ne-Myo-Aung, Myat-Kaung, Tint-Tint-Kyi et al., (2015): The safety of a conservative fluid strategy in adults with hospitalised with malaria; an observational study 7. World Health Organization, ( ): Global report on antimalarial drug efficacy and drug resistance

53 References 8. World Health Organization, ( ): Emergency response to artemisinin resistance in the greater Mekong subregion 9. Saw-Lwin,Micro-stratification in Pre-elimination and Elimination Phase 10.Saw-Lwin, Village Based Strategy (Stratification) 11.Renal involvement in severe malaria (Insein General Hospital ), Mar Mar Kyi, Myat Phone Kyaw, Myat Htut Nyunt, Tint Tint Kyi, Kyi May Htoo, Ne Myo Aung, Thinzar Cho Oo, Mi Mi Khine, Kyi Aye Thet 12.High frequency of clinically significant bacteremia in adults hospitalized with falciparum malaria, Phyo Pyae Nyein, Mar Mar Kyi, Ne Myo Aung et al. 13.Management of severe malaria, WHO, 2014

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