Fine-tuning Management in Dengue Fever

Fine-tuning Management in Dengue Fever Annual Scientific Meeting On Intensive Care 16 August 2014 Eg Kah Peng University of Malaya Medical Centre

Rise In Dengue Infection New Straits Times 8 July 2014 46,681 cases between Jan and now 87 people have died from the disease, a 222% increase in dengue deaths compared to the same period last year. http://www.nst.com.my/node/10919?m=1

Management of Dengue Fever 1. Making a complete diagnosis - phase of disease - warning signs - compensated/decompensated shock - evidence of organ impairment - complication of disease and/or treatment 2. Fluid management

CITIES» THIRUVANANTHAPURAM THIRUVANANTHAPURAM, June 3, 2013 Updated: June 3, 2013 14:08 IST C. MAYA DHS: follow fever management protocols Clinical mismanagement blamed for dengue deaths Clinical mismanagement of dengue fever has been leading to an increased mortality of cases in the State, especially as most of the suspected dengue deaths are being reported from small and medium private hospitals in the periphery. S. Ashwini Kumar, Professor of Medicine, Thiruvananthapuram Medical College, said that unnecessary fluid therapy, in the case of children, was a significant cause of mortality in dengue fever. What is required is a close monitoring of the clinical signs and symptoms of the patient and not the lab report which says that the platelet count has gone down. 4

Clinical course of dengue Dengue is a systemic and dynamic disease. PLATELET COUNT Dengue is NOT a PLATELET count disease 5

Dengue Classification (WHO 2009)

Days of illness: 0 1 2 3 4 5 6 7 8 9 10 Phases of dengue: Febrile Critical Recovery 6 Key features: 1. Temperature 40 38 Potential clinical issues 2. Oral intake 3. Urine output Dehydration Shock Bleeding Reabsorption Fluid overload Laboratory changes 4. WBC 5. Platelet 6. HCT Capillary permeability Organ Impairment Platelet WBC Haematocrit Viraemia IgM/IgG Virology and Serology Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 11

Case scenario 10 year old boy, weight 30kg Presented at day 3 of fever, vomiting and lethargy NS1 positive, wbc 5.3, PCV 0.37, platelets 204 Admitted to private medical centre Day 3-6 of illness: given IV drip 1/2NS alternate with 1/2NSD5% at 2-4ml/kg/hr Day 6: developed hypotensive shock, given NS 30ml/kg and referred to UMMC Accumulative I/O before transfer : +7000ml

On arrival to UMMC Alert, conscious Cold peripheries, reduced pulse volume BP 102/67mmHg, HR 110bpm, RR 40/min, SpO2 99% on air, temp 36.4 o C (last temp spike was 9 hours before arrival) Bilateral pleural effusion Liver 5cm palpable Urine output 0.8ml/kg/hr PCV 0.49, wbc 14.1, Plt 48 Evaluation : Severe dengue in compensated shock with excessive fluid accumulation - another 12-24 hours of plasma leakage

Problem: Shock 7 litres fluid How much fluid to give? What type of fluid? When to stop?

MODULE 8A: IV Fluid Principles http://www.wpro.who.int/emerging_diseases/documents/ dengue.clinical.management.package.v2/en/ Dengue Clinical Management Acknowledgements This curriculum was developed with technical assistance from the University of Malaya Medical Centre. Materials were contributed by the Ministry of Health, Singapore, the United States Centers for Disease Control and Prevention, and the University of Malaya Medical Centre.

Intravenous Fluid Administration the WHY s 1. Who should have IVF? 2. When to start? 3. When to stop? 4. How much should be IV? 5. What is the rate of IVF to be given? 6. What types of fluid? 16

Who should get an IV Fluid? 1. Those who are not able to drink enough to pee enough 2. Those with warning signs during the critical phase 3. Those with shock 18

What are important histories in dengue patients? 1. Date of onset of fever or illness History taking 2. Symptoms and severity 3. The 3 golden questions: How much oral fluid intake: quantity and quality? How much urine output: frequency, volume and time of most recent voiding? What activities can the patient do during the febrile illness? 4. Other fluid losses: diarrhoea, vomiting 5. Presence of warning signs

Pearls in clinical examination of dengue patients The 5-in-1 maneuver magic touch CCTV-R Hold the patient s hand to evaluate peripheral perfusion. Save life in 30 seconds by recognizing shock 1. Colour 2. Capillary refill 3. Temperature 4. Pulse Volume 5. Pulse Rate

Hemodynamic Assessment - Clinical Parameters Parameters Conscious level 3a. Organ perfusion (brain) Capillary refill time Extremities (color, temp) Peripheral pulse volume Heart rate (HR) Pulse pressure (PP) Blood pressure (BP) Respiratory rate (RR) Urine output 1. Peripheral perfusion 2. Cardiac output 4. Respiratory compensation for tissue hypoxia 3b. Organ perfusion (kidney) Holding the hands CCTV-R

Intravenous Fluid Administration 1. Who should have IVF? 2. When to start? 3. When to stop? 4. How much should be IV? 5. What is the rate of IVF to be given? 6. What types of fluid? 22

When to start and stop intravenous fluid therapy Febrile phase Limit IV fluids Early IV therapy may lead to fluid overload especially with non-isotonic IV fluid Critical phase IV fluids are usually required for 24 48 hours NOTE: For patients who present with shock, IV therapy should be <48 hours Recovery phase IV fluids should be stopped so that extravasated fluids can be reabsorbed 23

Natural history of plasma leakage in dengue Detected by Ultrasound - As early as day 2 of fever, subclinical. Peaks during critical phase, one day after defervescence In DF and DHF cases as well, mild plasma leakage may not cause hemoconcentration Most common pleural effusion and ascites, gall bladder wall edema Magnitude of plasma leakage is main determinant of severity Setiawan, J Clin Ultrasound 1995 Thulkar S, J Clin Ultrasound2000 Srikiatkhachorn, Pediatr Infect Dis J 2007 Statler J, J Clin Ultrasound, 2008 24

Intravenous Fluid Administration 1. Who should have IVF? 2. When to start? 3. When to stop? 4. How much should be IV? 5. What is the rate of IVF to be given? 6. What types of of fluid? 25

What type of intravenous fluid therapy should we use? Use isotonic solutions (normal saline, Ringer s lactate) Colloids are preferred if the blood pressure has to be restored urgently (e.g. Group C patients) 1,2,3 Solution Na K Cl Lactate Ca Osm meq/l Normal saline (NS) 154 154 292 D5% NS 154 154 565 Ringer s lactate 130 4 109 28 3 274 Hartmann s solution 131 5 111 29 2 278 1 Dung NM, Day NP, Tam DT. Clin Infect Dis, 1999, 29:787 794; 2 Ngo NT, Cao XT, Kneen R. Clin Infect Dis, 2001, 32:204 213. 3 Wills BA et al. N Engl J Med, 2005, 353:877 889. 26

What intravenous fluids should not be used? Hypotonic solution, e.g. 0.45% saline, even during the febrile phase Dextrose solutions should be limited to avoid hyperglycaemia, but may be used in hypoglycaemia with close blood glucose monitoring Albumin solutions Fresh frozen plasma 1 Platelet concentrates 1 1 Lum LCS et al, J Pediatr 2003;143:682-4. 27

Why isotonic fluids? 1 / 3 of Total Body Water 2 / 3 of Total Body Water What % of body weight is water? Vascular space ¼ of ECF Extracellular Fluid (ECF) Intracellular Fluid (ICF) 3 60 rd space to 70% of body weight is water, higher % in young children and lower % in adults and obese persons IV Infusion of Isotonic Fluid 1liter 0.9 NS 750 ml to 3 rd space 250cc (1/4) to vascular space IV Infusion of Hypotonic Fluid (low sodium) 1liter 0.45 NS 333 cc to ECF 83cc (1/12) to vascular space, the remainder to intracellular space 28

What happens in the critical phase? Fluid shifts in a capillary leak situation Contracted vascular space Expanded 3 rd space Expanded intracellular fluid (ICF) IV Infusion of Isotonic fluid 1 litre 0.9 NS IV > 750 cc to ECF << 250 cc (1/4) to vascular space IV Infusion of Hypotonic fluid (low sodium) 1 litre 0.45 NS 333 cc to 3 rd space << 83cc (1/12) to intravas space, remainder goes to ICF 29

Association between a Chloride-liberal vs Chloride-Restrictive IV fluid Administration Strategy and Kidney Injury in Critically Ill Adults 0.9% Saline 4% Gelatin 4% Albumin Plasmalyte Hartmann Sodium 150 154 140 140 129 Potassium 5 5 Chloride 150 120 128 98 109 Calcium 2 Magnesium 1.5 Lactate 29 Acetate 27 Gluconate 23 Nor Azim M Yunos, JAMA 2012 30

Association between a Chloride-liberal vs Chloride-Restrictive IV fluid Administration Strategy and Kidney Injury in Critically Ill Adults Chloride restrictive fluid resuscitation strategy was associated with significant reduction in AKI and use of renal replacement therapy Nor Azim M Yunos, JAMA 2012 31

Complications with too much 0.9% saline Hyperchloremic metabolic acidosis normal anion gap, low bicarbonate May be misinterpreted as worsening shock Reduced GFR - Acute Kidney Injury How to avoid these complications? Start with 0.9% saline, then switch to Hartmann s Solution Monitor serum chloride level or anion gap or bicarbonate 32

Electrolyte disturbances and abnormal urinalysis in children with dengue infection Lumpaopong et al, 2010 33

Colloid therapy in dengue shock When are colloids given? 1. Hypotensive shock 1,2,3 2. Repeated shock 2nd or 3rd shock and onwards 3. After >20 to 30 ml/kg of crystalloids 4. HCT does not decrease after crystalloid administration in shock state DOSE: Limited to 30 to 50 ml/kg/day 1 Dung NM, Day NP, Tam DT. Clin Infect Dis, 1999, 29:787 794; 2 Ngo NT, Cao XT, Kneen R. Clin Infect Dis, 2001, 32:204 213. 3 Wills BA et al. N Engl J Med, 2005, 353:877 889. 34

35 Why use colloid therapy in dengue shock? EFFECTS Stays longer in circulation Faster reduction in HCT 1-3 Restores cardiac index faster NOTE: If NO clinical improvement with reduced HCT, think significant occult bleeding SIDE-EFFECTS Allergic reactions Impair coagulation Potential renal impairment 1 Dung NM, Day NP, Tam DT. Clin Infect Dis, 1999, 29:787 794. 2 Ngo NT, Cao XT, Kneen R. Clin Infect Dis, 2001, 32:204 213. 3 Wills BA et al. N Engl J Med, 2005, 353:877 889.

Age-related microvascular permeability Filtration coefficient 3-4 x higher in young children Larger microvascular surface area per unit volume of skeletal muscle than adults. Novel microvessels more permeable to water and plasma proteins than when mature. Children more readily develop hypovolaemic shock than adults in DHF Gamble et al, Clinical Science,2000

Intravenous Fluid Administration 1. Who should have IVF? 2. When to start? 3. When to stop? 4. How much should be IV? 5. What is the rate of IVF to be given? 6. What types of fluid? 39

HOW MUCH & HOW FAST to run intravenous fluid? HOW MUCH & HOW FAST? Give the minimum IVF required to maintain good perfusion and urine output of about 0.5 ml/kg/hr Volume based on ideal body weight if overweight Titrate to haemodynamic state and age What does titrate IVF rate to haemodynamic state mean? Reassess haemodynamic responses immediately after every IV bolus Adjust the rate of IVF for the subsequent 1 hour or 2 to 4 hours 40

HOW MUCH & HOW FAST to run intravenous fluid? HOW MUCH & HOW FAST? Adult Compensated shock: 5 to 10 ml/kg over one hour Hypotensive shock: 10 to 20 ml/kg over 15 to 30 minutes Child Compensated shock: 10 to 20 ml/kg over 1 hour Hypotensive shock: 20 ml/kg over 15 to 30 minutes AFTER correction of shock: REDUCE IV infusion rate in step-wise manner whenever: Haemodynamic state is stable Rate of plasma leakage decreases towards end of critical phase indicated by: Improving haemodynamic signs Increasing urine output Adequate oral fluid intake Haematocrit decreases below baseline value in a stable patient 41

IV Fluid management (ml/kg/hr) Fluid titration in compensated shock 12 10 1 hrs 8 5-10 ml 2 ~ 3 h Deceleration rate 6 5-7 ml 4 ~ 7 h 4 3-5 ml 8~11 h 2 2-3 ml 36~42 h 2 ml STOP < 48 hrs 0 42

IV Fluid management (ml/kg/hr) Fluid titration in hypotensive shock 25 20 15 min 15 Deceleration rate 10 20 ml 1 hr 2 ~ 3 h 5 0 10 ml 7 ml 4~7 h 5-7 ml 8~11 h 12~24 h 3-5 ml 3-4 ml 25~36 h Stop <48 h 45

What do you do when there is no sustained response to IVF (cyrstalloid)? 47

Group C: Emergency treatment Compensated shock (systolic pressure maintained + reduced perfusion) Start isotonic crystalloid therapy 5 10 ml/kg/hr (adult) or 10 20 ml/kg/hr (child) for 1 hour *REASSESS Increasing or high HCT Not improved Check haematocrit After first bolus, if patient has not improved, check HCT. If HCT increases or is still high, give second bolus of crystalloid at 10 20 ml/kg/hr for 1 hour. Use colloid** if patient has already received several boluses of crystalloid. Crystalloid (2nd bolus) or colloid** 10 20 ml/kg/hr for 1 hour *REASSESS If improved Reduce IV crystalloids to 7 10 ml/kg/hr for 1 2 hours Continue step-wise reduction of IVF If not improved, recheck haematocrit *REASSESS If patient improves, reduce IVF rate to 7 10 ml/kg/hr for 1 2 hours, and continue step-wise reduction of IVF. If plasma leakage continues, further boluses may be required in the next 24 48 hours. If not improved, recheck haematocrit * Reassess the patient s clinical condition: vital signs, 5-in-1 magic touch, urine output; decide on the situation.

Group C: Emergency treatment bleeding? Compensated shock (systolic pressure maintained + reduced perfusion) Start isotonic crystalloid therapy 5 10 ml/kg/hr (adult) or 10 20 ml/kg/hr (child) for 1 hour After first bolus, if patient has not improved, check HCT. *REASSESS Not improved Check haematocrit If HCT decreases or is lower than baseline, look for severe bleeding (gastrointestinal haemorrhage, haematoma) Urgent blood transfusion Continue step-wise reduction of IVF YES Decreasing HCT?Severe overt bleed If severe bleeding is present, transfuse blood urgently, using 5 10 ml/kg packed red cells or 10 20 ml/kg fresh whole blood. Give colloid until blood becomes available. If patient improves after blood transfusion, continue step-wise reduction of IVF. * Reassess the patient s clinical condition: vital signs, 5-in-1 magic touch, urine output; and decide on the situation. ** Colloid is preferable if the patient has already received several boluses of crystalloid IV: intravenous, HCT: hematocrit, IVF: intravenous fluids

Group C: Emergency treatment bleeding? (cont.) Compensated shock (systolic pressure maintained + reduced perfusion) Start isotonic crystalloid therapy 5 10 ml/kg/hr (adult) or 10 20 ml/kg/hr (child) for1 hour *REASSESS Not improved Check haematocrit No improvement after first bolus, reduced HCT If NO Bleeding is evident Decreasing HCT Urgent blood transfusion Continue step-wise reduction in IVF YES Severe overt bleed No Colloid 10 20 ml/kg/hr If NO bleeding is seen, give colloid 10 20 ml/kg over 1 hour *REASSESS Improved Reduce IV colloids 7 10 ml/kg/hr for 1 2 hours Continue step-wise reduction in IVF *REASSESS Not improved Urgent blood transfusion If patient improves after colloids, continue step-wise reduction of IVF If patient has not improved, HCT would have decreased. Transfuse blood urgently (same volume as previous slide) * Reassess the patient s clinical condition: vital signs, 5-in-1 magic touch, urine output; and decide on the situation. ** Colloid is preferable if the patient has already received several boluses of crystalloid

Pearls: How to recognize severe bleeding Determine if the patient has UNSTABLE haemodynamic status Any ONE of the following: 1. Persistent and/or severe overt bleeding, regardless of the HCT level 2. A decreased HCT after fluid resuscitation, especially with colloids 3. Hypotensive shock with low/normal HCT before fluid resuscitation 4. Refractory shock 5. Persistent metabolic acidosis Remember that clinical signs come as a package. Mostly and likely, more than one of the above will be observed. Group and CROSS MATCH for all dengue SHOCK (esp Hypotensive) patients at admission 51

Emergency treatment of haemorrhagic complications Give: 5 10 ml/kg of fresh packed red blood cells or 10 20 ml/kg of fresh whole blood at appropriate rate Reduce colloid/crystalloid infusions, except to maintain euglycemia What is a good clinical response? Improving haemodynamic state vital signs, peripheral perfusion and urine output Improving acid-base balance When should you consider repeating blood transfusion? 1. Further blood loss 2. Unstable haemodynamic state 52

WHEN TO STOP? When to stop intravenous fluids? Knowing when is critical to dengue management Step-wise reduce IV infusion rate until it is stopped, same as in earlier slide. Definite stop: 1. Features of intravascular compartment overload a. Hypertension with good volume pulse b. Breathing difficulties, pulmonary oedema 2. 48 hours after defervescence 53

Managing shocked patient with fluid overload Don t stop IVF, but Go slow Use colloids 2 to 5 ml/kg/hr, reduce rate accordingly Maintain blood glucose within normal range Slow blood transfusion if necessary (blood is also volume), except when overt bleeding is severe WAIT (For what?) Pre-empt need for renal dialysis allopurinol, phosphate binders, potassium chelation 63

First, CCTVR must be good Then Stop all IVF How to use frusemide Then wait for 1-2 hours to see if CCTVR is still good, urine output may improve If urine is still not coming, but CCTVR is stable, then try a very small dose of frusemide, e.g. 0.2 mg/kg IV. Once urine flows, check CCTVR again to make sure it is good. Patient s breathing should be better after passing out some volume 64

Is this abdominal pain a warning sign? 65

Look at the big picture: Zoom Out (CONTEXT) 1. In which phase of illness febrile, critical or convalescent? 2. What was duration of IVF? 3. What volume of IVF has patient received? 4. How much was urine output? 5. How much is the positive fluid balance? Look for other signs of perfusion, CCTVR. Breathing, pleural effusion, ascites are affected by total fluid balance. JVP? Liver size increases? Treat the context, not the number the patient 66

Abdominal pain is due to fluid overload, Not a warning sign of shock. Fluid overload causes fluid congestion in liver; Gives rise to pain The more congestion, the more tender. All IVF must be stopped to prevent pulmonary edema 67

Summary of IV fluid therapy in dengue IVF therapy should be managed like drug therapy. No ideal IV solution, a combination may avoid complications of using exclusively one type of fluid Dynamic situation means frequent assessment and adjustment according to patient response or lack of response Not according to perceived protocol. 68

Hematocrit Monitoring And Dengue Summary of IV fluid therapy in dengue Inadequate Adequate Excessive Hypovolaemia Compensated shock Hypotensive shock Bleeding DIC Multi-organ failure Improved circulation and tissue perfusion Capillary refill <2 seconds Normal heart rate Normal blood pressure Normal pulse pressure Urine 0.5ml/kg/hr HCT to normal Improving acid-base Fluid overload: Pulmonary oedema Respiratory distress Worsening pleural effusion and ascites Clinical deterioration 69

To reduce dengue deaths Knowledge Dengue case management and of internal medicine Attitude Know our own limitations, seek help early Practice Basic medicine history, physical examination and careful non-invasive monitoring and charting of serial responses, lab parameters vs. high tech modern medicine

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