REVISED GUIDELINES ON FLUID MANAGEMENT OF DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER 2012 INTRODUCTION ‘A. Background Dengue fever (DF) and Dengue Hemorrhagic Fever (DHF)/Dengue Shock Syndrome (DSS) continue to be significant causes of morbidity and mortality in the Philippines. Dengue is considered to be endemic in the Philippines with clustering of cases and outbreaks occurring at unpredictable intervals due to inability to control and prevent this arthropod-bome disease After the release of the first Evidence-based Guidelines on Dengue Fever/Dengue Hemorrhagic Fever in 2008 by the Philippine Pediatric Society, the World Health Organization (WHO) published a document entitled “Dengue Guidelines for Diagnosis, Treatment, Prevention and Control- New edition 2009." This document, referred to hereafter as the 2009 WHO Dengue Guidelines, is a joint publication of the WHO and the Special Programme for Research and Training in Tropical Diseases (TDR) and was meant to supersede the recommendations in the 1997 WHO Dengue Guidelines.” ‘The 2008 WHO Dengue Guidelines presented a new Dengue case classification and a step-wise approach to the management of dengue. Due to the urgent need to provide standardized guidelines on clinical management for pediatricians and other practitioners, the Committee on Dengue developed the 2010 Interim Guidelines on Fluid Management of Dengue Fever and Dengue Hemorthagic Fever which primarily focused on the fluid management of patients with dengue hemorrhagic fever presenting with or without shock. A section comparing the standard case classification with the 2009 proposed WHO dengue case classification was included although results of the validation studies of the new case classification for dengue were not yet available at that time. Since then, several studies have shown the validity and_ practical usefulness of the new case classification for dengue, particularly in detecting severe cases. The 2010 PPS Interim Guidelines were posted in the PPS website on 18 October 2010. Shortly after, on 29 October 2010, the Department of Health (DOH) with support from the WHO conducted a National Dengue Workshop on Clinical Management to serve as a forum for the local adaptation of the 2009 WHO Dengue Guidelines. The PPS, represented by members of the Committee on Dengue were invited in this meeting. Results of the discussion during this national workshop paved the way for the development of a document which aimed to establish a standard in the diagnosis and management of dengue in all public and private health facilities and other stakeholders. The specific recommendations on fluid management for dengue patients contained in the 2010 PPS Interim Guidelines on Fluid Management of Dengue Fever and Dengue Hemorrhagic Fever were adopted in this document. This document became known as the DOH Revised Dengue Clinical Case Management Guidelines 2011. The revised guidelines were approved by the Secretary of Health, Dr. Enrique T. Ona on 12 March 2012 as Administrative Order No. 2012-0006." While the document which became the basis for the Administrative Order conceming the DOH Revised Dengue Clinical Case Management Guidelines 2011 was being finalized, the WHO Regional Office for South-East Asia published a document entitled Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Hemorhagic Fever: Revised and Expanded Edition 2011.° This latest document presented a different approach to the fluid management of dengue patients with or without shock. The document also used the standard WHO casedefinitions for dengue fever (Undifferentiated Fever, Dengue Fever, Dengue Hemorrhagic Fever/Dengue Shock Syndrome) plus an additional clinical syndrome called Expanded Dengue ‘Syndrome. In the light of new information from the validation studies for the new Dengue Case classification and the 2011 WHO-SEA Regional Office Comprehensive Guidelines, the PPS Committee on Dengue met on 24 August 2012 for the purpose of comparing all the available documents, examining the available evidence from the published reports, and coming up with a document that the group felt will be more appropriate and acceptable to the clinicians. ‘A Clinical Practice Guideline to update the 2008 PPS evidence-based guidelines of DF/DHF is being planned because additional data from new randomized controlled trials, systematic reviews and meta-analysis has become available since the release of the 2008 PPS practice guidelines. A CPG on dengue will be able to examine all available evidence to answer relevant clinical questions. Until the updated CPG becomes available, the purpose of this document is to provide a brief discussion on the new dengue clinical case classification and to present revised guidelines on fluid management based on the level of severity. B. Objectives The main objectives of these 2012 Revised Guidelines on Fluid Management of DF/DHF are the following 1. To compare the WHO 1997 Dengue Case Classification and the WHO-SEARO 2011 Dengue Case Classification with the DOH 2011 Revised Dengue Case Classification 2. To update the section on fluid management 3. To revise the clinical algorithms on fluid resuscitation of patients with dengue based on presenting clinical features and based on the presence or absence of warning signs and shock C, Target Population ‘These 2012 Revised Guidelines on Fluid Management for DF/DHF have been developed for use by pediatricians, family physicians, general practitioners, and other healthcare professionals of various specialties both in the private and govemment settings who are involved in the diagnosis and management of patients with dengue. It provides a stepwise approach on the fluid management of dengue patients where treatment and subsequent referral to hospitals and to facilities with intensive care units is based on the severity of illness. DENGUE CASE CLASSIFICATION Dengue is disease with a wide spectrum of clinical presentation often with unpredictable clinical progression and outcome. It is often difficult to predict the subset of patients who will progress from non-severe to severe disease. Early recognition of patients who may rapidly develop more severeclinical disease is crucial in order to facilitate hospital admission or referral and institute urgent management. ‘The WHO 1997 Dengue case classification? which is still in current use, was formulated by the Technical Advisory Committee at its meeting in Manila, Philippines in 1974 and was largely based on the pioneering studies in Thailand in the 1960's. Few modifications have evolved through the years but the case definition and classification remained to be essentially the same. In the WHO 1997 dengue case classification, symptomatic dengue virus infections are grouped into three categories: undifferentiated fever, dengue fever (OF), and dengue hemorhagic fever (DHF). Dengue hemorrhagic fever is further classified into four severity grades, with grades III and IV being classified ‘as dengue shock syndrome (DSS), Based on the WHO 1997 dengue case classification, DHF cases must fulfil all the following four criteria: (1) Fever or a history of acute fever lasting 2-7 days; (2) hemorrhagic tendencies evidenced by at least one of the following: a positive tourniquet test (TT); petechiae, purpura, ecchymoses; bleeding from mucosa, gastrointestinal tract, injection sites, or other location; (8) thrombocytopenia, defined a platelet count < 100,000/u!; (4) hemoconcentration defined ‘as > 20% rise is hematocrit relative to baseline or evidence of plasma leakage (i.e. pleural effusion, ascites, and/or hypoproteinemia), Diversity in and the changing dengue epidemiology in different countries in recent years led to problems with the use of the existing WHO classification. Several authors have reported difficulties, and inconsistencies in this classification with failure to fulfil all four criteria for the definition of DHF in severe dengue cases."'*° As a result, patients with clear evidence of vascular leakage who lack one of the other prerequisites are categorised inappropriately as DF. Possible consequences of this is underreporting of DHF and delayed or inappropriate management leading to high mortality rates. This has led to reassessment of the WHO case classification. In 2008, a consortium of experienced dengue clinicians and scientists came together as the Dengue Control (DENCO) Study Group and set ‘out to evaluate the existing WHO 1997 dengue classification across all age groups and a wide ‘geographical range and to develop a revised evidence-based classification that would better reflect Clinical severity. "° Results of the multicenter prospective study conducted in 2259 patients with clinically suspected dengue recruited at 11 hospitals in 7 countries in South-east Asia and Latin America showed that applying the WHO 1997 dengue case definition of DHF/DSS to distinguish between cases requiring major intervention and those not requiring major intervention had a sensitivity and specificity 76% and 54%, respectively. Twenty two (22%) of patients with shock did ‘ot fulfil all the criteria for dengue haemorrhagic fever. Inclusion of readily discemible complications (shock / severe vascular leakage and / or severe bleeding and / or severe organ dysfunction) to identify patients with severe dengue requiring major intervention resulted in higher sensitivity and specificity, 96% and 97% respectively. This was the basis for the revised classification system ‘comprised of two entities, ‘Dengue’ and ‘Severe Dengue’, which was incorporated into the WHO 2009 dengue classification. The large group of patients with Non-severe Dengue was further subdivided into two subgroups: patients with warning signs and those without warning signs. The validity and Usefulness of the revised classification was later confirmed in several studies comparing the WHO 1997 dengue classification with the new WHO 2009 dengue classification '"”" In the WHO-SEARO 2011 Comprehensive Guidelines, the case definitions for Undifferentiated Fever, Dengue Fever, Dengue hemorrhagic Fever and Dengue Shock Syndrome are the same as the WHO 1997 dengue case definitions, although with the addition of ‘Expanded Dengue Syndrome’, defined {as presence of unusual manifestation in patients with severe organ involvement such as liver, kidneys brain or heart in association with dengue infection.” This definition is actually similar to the classification of Severe Dengue with organ impairment in the WHO 2009 dengue case classification. ‘The document emphasizes that Dengue fever and Dengue Hemorrhagic Fever are different clinical conditions from the beginning of the illness and that Dengue fever, however badly managed will never progress to Dengue Hemorrhagic Fever.In the DOH Revised Dengue Clinical Case Management Guidelines 2011, dengue is classified as Dengue without Waming signs, Dengue with Waming signs and Severe dengue. Based on the WHO 2009 dengue classification, Severe dengue includes those with severe plasma leakage, severe bleeding or severe organ impairment. The definitions and criteria for the above classifications were locally adapted as a result of discussions during the meetings following the National Dengue Workshop in 2010. The new DOH dengue case classification and levels of severity are compared with the WHO1997/2011 Case classification and are presented in Table 1. There are dengue experts who fee! that while the new case definition may be useful for surveillance, reporting, and risk classification, it does not take into consideration the different pathophysiology for the clinical manifestations of dengue, for example bleeding and shock.“ Therefore, it is recommended that pediatricians and other linicians be familiar with both classifications. Furthermore, many private and government insurance systems are yet to be informed of the new dengue classification. Therefore, it is advised that when writing the diagnosis in the patient's medical records, both the standard and the new classification should be written, Table 1. Comparison of the WHO 1997/2011 Case Definition and Case Classification for Dengue with the Revised DOH Dengue Case Classification WHO 1997/2011 Case Definition of Dengue and Levels of Severity Revised DOH/PPS Classification and Levels of Severity 2011 Case Definition for Dengue Fever Probable ‘an acute febrile illness with 2 or more of the following Headache Retro-orbital pain Arthralgia Rash Hemoragic manifestations Leukopenia; AND ‘Supportive serology ( a reciprocal Hl antibody ter > 1280, a comparable IgG assay ELISA titer or (+) igM antibody test on a late or acute convalescent phase ‘serum specimen Confirmed: ‘A.case confirmed by laboratory criteria Case Definition for Dengue without Warning Signe Probable dengue: Lives in or travels to dengue-endemic area, with fever, plus any two of the following ‘© Headache © Body malaise = Myalgia © Arthralgia ‘+ Retro-orbital pain = Anorexia © Nausea = Vomiting © Diarthea ‘© Flushed skin ‘© Rash (petechial, Herman's sign) 5 Tourniquet test postive AND ‘+ Laboratory test, atleast CBC (leukopenia with or without thrombocytopenia) andior dengue NS1 antigen test or dengue IgM antibody test (optional). Confirmed dengue: © Viral culture isolation + POR Case Definition for Dengue Hemorrhagic Fever (DHF) Case Definition for Dengue with Warning Signs: Lives in or travels to dengue-endemic area, with fever lasting for 2-7 days, plus any one of the following‘The following rust allbe present 1. Fever, or history of fever, lasting for 2-7 days, occasionally biphasic 2. Hemorrhagic tendencies evidenced by at least one of the following 2. (+) tourniquet test b. Petechiae, ecchymosis, purpura ©. Bleeding from the mucosa, GIT, injection sites or other locations 4. Hematemesis or melena 3. Thrombocytopenia ( 100,000 celisimm® or less) 4. Evidence of plasma leakage due to Increased vascular permeability, manifested by at least one ofthe following: a. Arise in the hematocrit equal to or {greater than 20% above average for age, sex, and population b.Adrop in the hematocrit following volume replacement treatment ‘equal to or greater than 20% of baseline ©. Signs of plasma leakage such as, pleural effusion, ascites and hhypoproteinemia Case Definition for Dengue Shock syndrome (pss) All of the four criteria for DHF must be present plus evidence of circulatory failure manifested by: Rapid and weak pulse, AND Narrow pulse pressure ( < 20mmHg [2.7kPa] OR manifested by. Hypotension for age, AND Cold clammy skin and restlessness * Abdominal pain or tenderness + Persistent vorniting * Clinical signs of fluid accumulation + Mucosal bleeding + Lethargy, restlessness + Liver enlargement * Decreased or no urine output within 6 hours’ + Laboratory: increase in Het andlor decreasing platelet count Confirmed dengue: + Viral culture isolation * PCR Grading of Severity of DHF/OSS DHF Grade 1 Fever accompanied by non-specific constitutional signs and symptoms such as anorexia, vomiting, abdominal pain; the only hemormagic. manifestation 's 2 (+) tourniquet test and/or easy bruising DHE Gra ‘Spontaneous bleeding in addition to manifestations (of grade 1 patients usually in the form of skin or ther hemorrhages ( mucocutaneous), GIT DHE Grade 3 (DSS) Circulatory fallure manifested by rapid. weak pulse ‘and narrowing of pulse pressure or hypotension, with ‘the presence of cold clammy skin and restlessness Case Definition for Severe Dengue Lives in or travels to a dengue-endemic area with fever of 2~ 7 days and any of the above clinical manifestations for dengue with or without warning signs, plus any of the following: + Severe plasma leakage, leading to = Shock = Fluid accumulation with respiratory distress + Severe bleeding + Severe organ impairment = Liver: AST or ALT 2 1000 = GNS: eg, seizures, impaired consciousness — Heart: eg, myocarditis = Kidneys: e.g, renal failure Note: ‘Above manifestations and/or laboratory parameters require Strict observation, monttoring, and appropriate medical intervention. 77 | Revsrdberge Gace coe 207 EEDHF Grade 4 (DSS) Profound shock with undetectable blood pressure or pulse * Decreased or na urine output within 6 hours was added by the PPS Canvmflee on Dengue as another warring ign I FLUID MANAGEMENT OF DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER A Fluid management for patients with DF/DHF (Dengue without warning signs) who are not admitted. Obtain a reference complete blood count (CBC). Leukopenia (WBC <5000 cellsimms) is helpful in making early diagnosis of dengue infection and lasts throughout the febrile period. A sudden rise in HCT is usually observed simultaneously or shortly after the drop in platelet count Hemoconcenration or rising HCT is objective evidence of plasma leakage.” In patients with DF/DHF Grade | who are not admitted, oral rehydration solution should be given as follows based on weight, using currently recommended ORS: Table 2. Calculation of Oral Rehydration Fluids Using Weight (Ludan Method)"® Body Weight (kg) ‘ORS to be given > 3-10 100 mifkgiday > 10-20 75 mlkgiday > 20-30 50-60 mi/kg/day > 30-60 40-50 mlkg/day Reduced osmolarity ORS containing sodium 50-75 mmoliiter. ‘Sports drinks [Na] <20 meqs/should not be given Fluid management for patients who are admitted, without shock (DF/DHF Grade ll or Dengue without warning signs). Obtain a reference CBC. Isotonic solutions (D; LRS, Ds Acetated Ringers Ds NSS/ Ds 0.9 NaCl) are appropriate for DHF Patients who are admitted but without shock. Give only isotonic solutions such as 0.9% NaCI (saline) or Ringers Lactate with or without glucose For infants < 6 mos old, DS 0.45 NaCI is preferable ("DS 0.45 NaCl Is prepared by mixing equal volumes of D5 0.9 NaCL and DSW). Do NOT use hypotonic fluids (e.g. 05.0.3 NaCl) Maintenance IVF is computed using the caloric-expenditure method (Holliday and Segar Method)"* or Calculation Based on Weight (Ludan Method) ® Table 3. Calculation of Maintenance Intravenous Fluid Infusions (Holliday and Segar Method)"*Body Weight (ka) Total Fluid Requirement (ml/day) 3-10 100 milkg, > 10-20 kg 1,000 mi + 50 ml/kg for each kg > 10 kg > 20 1,500 mi + 20 ml/kg for each kg > 20 kg ‘+ If the patient shows signs of mild dehydration but is NOT in shock, the volume needed for mild dehydration is added to the maintenance fluids to determine the total fluid requirement (TFR). ‘* The following formula may be used to calculate the required volume of intravenous fluid to infuse: TER = Maintenance IVF + Fluids as for Mild dehydration" ‘+ Where the volume of fluids for mild dehydration is computed as follows:"” infant (age<12months) 50 ml/kg Older Child or Adult (age>12 months) 30 ml/kg ‘+ The computed volume is given over 24 hours. ‘+ Sample computation for a 10 kg patient with dengue and mild dehydration Step 1: Compute for Total Fluid Requirement: TFR= Maintenance Fluids + Fluids for Mild dehydration (100 x 10kg) + (50 x 10kg) = 1000 + 500 }500 mi Step 2: Volume computed to be given over 24 hours TFR = 1,500 ml 24 hrs, = 62 mi/he (6 mlkgihr) CONSTANT, PERIODIC REASSESSMENT IS NEEDED. FLUID RATE SHOULD BE ADJUSTED ACCORDING TO THE CLINICAL CONDITION, VITAL SIGNS, URINE OUTPUT AND HEMATOCRIT LEVELS. Clinical parameters should be monitored closely and correlated with the hematocrit. This will ensure adequate hydration, avoiding under and over hydration. ‘+ _ Ifthe patient shows signs of deterioration, see Management for Compensated or Hypotensive ‘Shock, whichever is applicable ‘+ To compute for the fluid requirement of overweight patients, use the IDEAL BODY WEIGHT. + The MAINTENANCE fluids should not exceed 3 liters per day. C. Fluid management for patients who are admitted with Warning Signs but without shock © Obtain a reference CBC and HGT before fluid therapy. ‘+ Give only isotonic solutions such as 0.9% NaCl (saline) or Ringer's Lactate with or without glucose‘+ For infants < 6 mos old, DS 0.45 NaCI" is preferable if available (“D5 0.45 NaCl is prepared by mixing equal volumes of DS 0,9 NaCL and DSW ‘+ May give glucose containing IVF (D5) in the following conditions: = HGT < 80 mgidL ~ if HGT is not available and patient is unable to eat and is weak-looking ‘+ Rate of infusion is as follows: Start with 5-7 mlkg/hour for 1-2 hours, then © reduce to 3-5 m/kg/hr for 2-4 hours, and then © reduce to 2-3 m/kgihr or less according to clinical response ‘+ Reassess the clinical status and repeat the complete blood count (CBC) ‘+ Ifthe hematocrit remains the same or rises only minimally, continue with the same rate (2-3 mi/kg/hr) for another 2 - 4 hours. ‘© If there are worsening of vital signs and rapidly rising hematocrit, increase the rate to 5-10 mifkg/hour for 1-2 hours. 1. Reassess the clinical status, repeat hematocrit and review fluid infusion rates accordingly. 2. Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 mi/kg/hr. Intravenous fluids are usually needed for only 24 to 48 hours 3. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. This is indicated by: = urine output and/or oral fluid intake is/are adequate, or = HCT decreases below the baseline value in a stable patient ‘+ Laboratory investigations (ABCS) should be carried out in both shock and non-shock cases when ‘no improvement is registered inspite of adequate volume replacement (See Table 5). ‘Table §. Laboratory Investigations (ABCS) for patients who present with profound shock or have complications, and in cases with no clinical improvement inspite of adequate volume replacement Laboratory ‘Abbreviation laveetpeten Note ‘AAcidoss ‘Blood gas (capilary or | Indicate prolonged shock. Organ venous) involverient should also be looked into liver function and BUN, creatinine. B= Bleeding ‘Complete blood count | ITHCT decreases in comparison with the previous value or net rising, do cross- match for possible blood transfusion. C= Calcium Electrolyte, Care Fiypocalcemia is found in almost al cases ‘of DHF but asymptomatic. In more severe/complicated cases, Ca supplement is indicated at a dosage of * ml, dilute two times, IV push slowly, may be repeated every six hours, if needed (max. dose 10, ml of Ca gluconate},D= Blood sugar ‘Blood Sugar Most severe DHF cases have poor appetite together with vomiting. Those with impaired liver function may have hypoglycemia ‘Some cases may have hyperglycemia ‘SourGe: WHO-SEARO Gomprehense guidelines for prevention and contol of dengue and dengue haemorhagi fever. Revised and expanded edon. 2011 D. Fluid management for pati my nts adi ‘Compensated shock (systolic BP maintained but has signs of plasma leakage (hemoconcentration or reduced perfusion) + support BOX A. Obtain baseline CBC (a). Fluid resuscitation with plain isotonic crystalloid 10 ml/ ka/ hour over 1 hour. Give oxygen Yes | BOX B. IV crystalloid 5-7 mi/kg/hr for 1-2 hours, then reduce to 3-5 mi/kgihr for 2-4 hours; reduce to 2-3 ml/kg/hr for 2-4 hours, Maintenance fluids should not exceed 3 liters per day to avoid fluid overload (see Appendix A and B), If feasible, monitor HCT every 8-12 hours or as necessary (a) Reassess hemodynamic status frequently (see Table 6) including urine output (f) Monitor for signs of bleeding 1 If patient is stable and HOT increases by 10% from baseline, correlate clinically and assess need to increase fluid rate. If patient is unstable and HCT increases, go to Box B. If patient is unstable and there is a ‘sudden drop in HCT, look for signs of bleeding. Consider transfusion with fresh whole blood 20mikg or PRBC 10 mlikg, Improvement (b) d to the hospital with Compensated Shock (DHF Grade (See Table 6) No Repeat CBC [a] HT t or High Het BOX BOX D Administer 2" bolus of fluid, colloid/crystalloid (c) 40 mikgihr in + hour Patient is stable HCT decreases Goto Box B ¥ Patient is urlstable parameters If there are signs of occult/ overt bleeding initiate transfusion with fresh whole blood 20mikg or PREC 10mi/kg Reassess hemodynamic status and bleeding HCT increases Perform ABCS _ (see Table 5) B. ’ Administer 3° bolus of fluid (colloid) 10 mi/kgihr for 1 hour) If improved go to Box 2. If patient does not improve, go to Box E. If patient improves, go to Box B \f patient is stable for 48 hours, ‘stop IVF or give maintenance fluids or ORS (refer to Table 3 or Table 4). vida] inOtrOpeS (d) and Box E. If patient does ‘not improve, consider refer to tertiary centerE, Fluid management for patients admitted to the hospital with Hypotensive Shock (DHF Grade Ivipss) Hypotensive shock (e) 1 BOX A. Obtain baseline CBC (a). Fluid resuscitation with 10ml/kg plain isotonic crystalloid or colloid over 15 minutes (c). Give oxygen support. — BOX B. Crytalloid/colloid 10 mikg/hr for 1 hour, then continue with: 5-7 mifkgihr for 1-2 hours; reduce to 3-5 mi/kgihr for 2-4 hours; reduce to 2-3 mikkgihr for 2-4 hours. Maintenance fluids should not exceed 3 liters per day to avoid fluid overload (see Appendix A and B). It feasible, monitor HCT every 6 hours or as necessary. Reassess hemodynamic status frequently (see Table 6) including urine output (A) Monitor for signs of bleeding 1. If patient is stable and HCT increases by 10% from baseline, correlate clinically and assess need to increase fluid rate. 2. If patient is unstable and HCT increases, go to Box B. 3. If patient is unstable and there is a sudden drop of HCT, look for signs of bleeding. Consider transfusion with fresh whole blood 20 mivkg or PRBC 1OmUkg Improvement (b) (See Table 6) | No Repeat CBC (a) I HT 7 or High Het BOX C. Administer 2°° BOX D bolus fluid (colloid) 10 If there are signs of occult/ ml/kg over 15 min. Check covert bleeding initiate hemodynamic parameters transfusion with fresh whole (see Table 6) blood 20mvkg or PRBC 1Ombkg, Reassess hemodynamic status and bleeding + parameters Patient is stable Patient is unstable HCT decreases HCT increases 1. If improved go to Box B. Perform ABCS. (see Table 5) 2. If patient does not Reduce IVF rate to 7-10 milkgihr for 1-2 hrs improve, go to Box E. v Administer 3" bolus (colloid) 10 mikg for 1 hour) (¢) If patient remains stable, go to Box If patient improves, Box E. If patient does go to Box B not improve, consider 4. If patient is stable for 48 hours, stop IVF or give maintenance fluids or ORS (refer to Table 3 or Table 4), inotropes (d) and eli refer to tertiary centerTable 6: Hemodynamic Assessment: Continuum of Hemodynamic Changes Parameters Stable Condition | Compensated Shock | Hypotensive Shock ‘Sensorium Clear and lucid Clear and lucid (shock | Change of mental can be missed if you | status (restless and do not touch the combative) patient) Capillary refil ime Brisk (<2 se) Prolonged ©2866) Very prolonged, | mottled skin Extremities Warm and pink Cool peripheries [Cold and clammy Peripheral pulse Good volume ‘Weak and thready | Feeble or absent Heart rate Normal for age Tachycardia ‘Severe tachycardia with bradycardia in the late shock. Blood pressure Normal for age Normal systolic Narrowed pulse Normal pulse pressure but rising pressure (<20 mmHg) pressure for age diastolic pressure. Hypotension (see Narrowing pulse definition below) pressure. Unrecordable BP Postural hypotension _| Metabolic Acidosis, Respiratory rate Normal for age ‘Tachypnea Hyperpnea, Kussmaul breathing ‘Source: WHO and Special Programme for Research and Training in Tropical Diseases. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control 200: ANNOTATIONS: a. The white blood cell (WBC) count may be normal or with predominant neutrophils in the early febrile phase. Thereafter, there is a drop in the WBC count and neutrophils towards the end of the febrile phase, Leukopenia (WBC $5000 cells/mm3) usually precedes thrombocytopenia or risng HCT and is. helpful in predicting the critical period of plasma leakage. A sudden rise in HCT is usually observed at least 48 hours prior to or simultaneously with the drop in platelet count, Hemoconcentration may be demonstrated by an increasing level of HCT inspite of hydration. Hemoconcenration or rising HCT is objective evidence of plasma leakage.” If CBC is not readily available, assess hemodynamic status of patient using parameters in Table 6. b. Assessment of improvement should be based on 7 parameters: mental status, heart rate, blood pressure, respiratory rate, capillary refill ime, peripheral blood volume, extremities as described in Table 6, ©. Crystalloids (Ringer's lactate or 0.9 NaCI solutions) have been shown to be safe and as effective as colloid solutions (dextran, starch, or gelatin) in reducing the recurrence of shock and mortality Crystalloids are comparable to colloids in terms of total amount of fluids used in resuscitation and need for both rescue fluid and diuretics so they should be used as first ine in fluid resuscitation inmoderately severe (compensated) dengue shock.'**! Compared with crystalloids, colloids are associated with increased risk of allergic reactions and new bleeding manifestations?’ and are more expensive. Although there is insufficient data to ascertain the advantage of one type of fluid in cases of severe dengue shock (DHF grade |V) or hypotensive (uncompensated) shock, colloids may be used in patients who primarily present with hemodynamic instability and as rescue fluids in those whose cardiovascular status do not improve after the initial fluid resuscitation. Crystalloids 0.9% saline [normal saliney/ NSS + Normal plasma chloride ranges from 95 to 105 mmol/L. 0.9% Saline is a suitable option for initial fluid resuscitation, but repeated large volumes of 0.9% saline may lead to hyperchloremic acidosis. Hyperchloremic acidosis may aggravate or be confused with lactic acidosis from prolonged shock, Monitoring the chloride and lactate levels will help to identify this problem, When serum chloride level exceeds the normal range, it is advisable to change to other alternatives such as Ringer's Lactate. Ringer’s Lactate + Ringer's Lactate has lower sodium (131mmol/L) and chloride (11SmmolL) contents and osmolality of 273mOsmi/L. It may not be suitable for resuscitation of patients with severe hyponatremia. However, it is a suitable solution after 0.9 Saline has been given and the serum chloride level has exceeded the normal range. Ringer's Lactate should probably be avoided in liver failure and patients taking metformin where lactate metabolism may be impaired Colloids ‘©The types of colloids are gelatin-based, dextran-based and starch-based solutions. One of the biggest concems regarding their use is their impact on coagulation. ‘* Dextrans may bind to von Willebrand factor/Factor VII complex and impair coagulation the most However, this was not observed to have clinical significance in fluid resuscitation in dengue shock. Dextran 40 can potentially cause an osmotic renal injury in hypovolemic patients. Maximum dose of Dextran 40 is 30 milkg/day and for Voluven the maximum dose is 50 mikg/day. Gelatin has the least effect on coagulation among all the colloids but the highest risk of allergic reactions. Inotropes ‘The use of inotropes should be decided on carefully and it should be started after adequate fluid volume has been administered. + To calculate the AMOUNT of Dopamine to be added to 100 ml of IV base solution mg of Dopamine = 6 X desired dose meg/kg/min] X weightlkgl desired fluid rate [ml/h] + To calculate the VOLUME of drug to be added to 100 mi of IV base solution M1 of Dopamine = ma of drug [determined using formula above! ‘concentration of drug (mg/ml) Preparation of Dopamine: 40 mg/ml, 80 mg/ml Hypotension is defined as Systolic blood pressure of <9 mmHg or mean arterial pressure <70 mmbg in adults or a systolic blood pressure decrease of >40 mmHg of <2 standard deviation below normal for age; In children below 10 years of age the 5" centile for systolic blood pressure can be determined by the formula: Systolic Blood Pressure = 70 + [age in years X 2] mmHgUrine output ‘A good urine output indicates sufficient circulatory volume and may be used as an index or guide for decreasing the amount of fluid administered. An adequate urine output is at least 1 mlkg/hr and urine specific gravity of 1.020 is ideal. However in the WHO Dengue Guidelines “* a urine output of 0.5 cc/kgihr is considered acceptable and may have been chosen to avoid congestion in the course of the disease. Monitor urine output hourly until, the patient is out of shock, then 1-2 hourly Deliberate observation for a possible acute kidney injury’ acute renal failure must also be taken IV, FLUID MANAGEMENT IN CASES OF FLUID OVERLOAD, ENCEPHALOPATHY, AND MYOCARDIAL DYSFUNCTION A. Fluid Overload? + Review total IVF given. Stop administration of all hypotonic solutions. + Check and correct for ABCS (See Table 5) + Insert urinary bladder catheter to monitor hourly urine output. + Inthe Early stage of fluid overtoad (see Appendix B) © Switch from crystalloid to colloid as bolus infusions of 10miikg, not to exceed the acceptable total daily dose (Dextran 40 total daily dose S0m/kg/day or Voluven total daily dose 50 mikg/day) + Inthe Late stage of fluid overtoad (see Appendix B): © If'with stable vital signs: Give IV Furosemide 0.5 to 1mg/kg/dose; monitor VS every 15 minutes for one hour after furosemide to assess response © If in shock despite clinical signs and symptoms of fluid overtoad: Give 10mV/kg/hr of colloid * once with BP is stable, administer IV furosemide 0.5 to tmg/kg/dose; Continue with Dextran infusion until completion. Reduce IV fluids to as low as Ambkgihe. + If BP is unstable, check ABCS and other electrolyte imbalance. © May give repeated doses of furosemide if no urine output © Check intravascular volume status. Consider CVP insertion, © Check renal status to rule out acute renal failure. if oliguric renal failure is established, immediate referral to nephrologist for possible dialysis. B. Encephalopathy* © Consider patients with DF/DHF who present with convulsion and/or coma to have encephalopathyMay result from intracranial hemorhage, occlusion associated with DIC, metabolic abnormalities (hyponatremia) , or hepatic encephalopathy Management of Hepatic encephalopathy: © Reduce IVF; total IVF should not exceed 80% of fuid maintenance © In-cases with severe plasma leakage, use colloid if HCT continues to rise ‘Administer furosemide if with fluid overload Maintain proper head position at 30 degrees Give oxygen therapy to maintain adequate airway oxygenation Early intubation to avoid hypercarbia and to protect the airway © Decrease ammonia production: give lactulose 5-10 ml every 6 hours; systemic antibiotics to decrease bowel flora Maintain blood sugar levels at 80-100 mg/dl Correct acid base and electrolyte imbalance (correct _hypo/hypemnatremia, hypo/hyperkalemia, hypocalcemia, acidosis) © Administer IV Vitamin K: 3 mg for 5- year-old and adult patients. © Transfuse blood, preferably freshly packed red cells, as indicated. Avoid transfusion of platelets and fresh frozen plasma because it may cause fluid overload and cause increased ICP. Anticonvulsants should be given for control of seizures: phenobarbital, dilantin and diazepam IV as indicated, Empiric antibiotic therapy for suspected superimposed bacterial infections, © Ha-blockers or proton pump inhibitor may be given to alleviate gastrointestinal bleeding, © Avoid unnecessary drugs, particularly those metabolized by the liver, Consider plasmapheresis or hemodialysis or renal replacement therapy in cases with clinical deterioration C. Cardiac Involvement Cardiac involvement in Dengue Fever and Dengue Hemorrhagic Fever may be seen during the period of shock and during the period of convalescence, Variable manifestations may be seen from arrhythmias to evidence of systolic or diastolic dysfunction presenting as heart failure and/or shock, When a child with DHF presents with shock despite adequate volume replacement, especially if HCT is normal and CVP is normal or increased, then a cardiac evaluation is needed and a referral to a pediatric cardiologist is recommended. Laboratory examinationshould include an echocardiogram, ECG, chest x-ray and CPKMB. Echocardiogram will disclose systolic or diastolic dysfunction as well as the loading condition of the heart © Management of patients with Myocardial dysfunction ‘© Myocardial dysfunction should be treated with inotropes like dopamine, dobutamine or their combination for systolic dysfunction and milrinone for diastolic dysfunction, © Judicious fluid replacement with constant regular reassessment of hemodynamic status is needed for patients with myocardial dysfunction in order to prevent fluid overload and its complications. In patient with heart failure, fluids should be ‘computed 50-75% of maintenance depending on the degree of heart failure. In patients with uncompensated shock due to hypovolemia but with heart failure, the recommendation for fluid boluses should be followed. At any point fluid overload is considered, furosemide should be given once BP is stable (see management of Fluid overload) © If DF or DHF is complicated by myocarditis in the convalescent phase, bed rest is recommended. In addition, physical activity after discharge is restricted anywhere from 2 to 4 weeks up to 6 months depending on severity of the myocarditis. ‘+ Management of Cardiac Arrhythmias During the period of convalescence, variable arrhythmias observed range from sinus node dysfunction (sinus bradycardia, junctional rhythm), conduction abnormalities like first degree AV block, Wencheback and occasional PAC’s or PVCs, ECG documentation of these arrhythmias is recommended. Additional laboratory examination which may be done are cardiac enzymes (CPKMB) and chest x-ray. If PVC's are seen, serum electrolyte determination is recommended and hypokalemia should be corrected when present In patients with cardiac arrhythmia but with no signs of heart failure, there is no specific fluid requirement and the recommended fluid replacement therapy should be followed with constant regular reassessment of hemodynamic status in order to prevent fluid overload and its complications. Usually no treatment is needed for these benign arrhythmias but when available, a pediatric cardiology consult should be sought to guide management and can be reassuring, V. Criteria for discharging patients All of the following must be present: A. Clinical No fever for 48 hrs. Improvem ent in clinical status (general well-being, appetite, hemodynamic status, UO, no respiratory distress) ‘= Minimum of 2-3 days have elapsed after recovery from shock B. Laboratory ‘+ Increasing trend of platelet count Stable hematocrit w/o IVF PPS | evsed Derg Galen 01 04 0110, "1 12 13. 14. 15, REFERENCES Evidence-based Guidelines on Dengue Fever/Dengue Hemorrhagic Fever. Philippine Pediatric Society 2008, World Health Organization and the Special Programme for Research and Training in Tropical Diseases. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. New edition 2009, WHO/HTMINTD/DEN/2009.1 Technical Advisory Committee. Dengue hemorrhagic fever: diagnosis, treatment, prevention, and control. Geneva: World Health Organization, 1997. Administrative Order No. 2012-0006. DOH Revised Dengue Clinical Case Management Guidelines 2011 WHO- South-east Asia Regional Office, Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. Revised and expanded edition. 2011 Gupta et al, Assessment of World Health Organization definition of dengue hemorrhagic fever in North India, J Inf Dev. Countries 2010; 4 (3): 1650-155. Phuong CX, Nhan NT, Kneen R et al. Clinical Diagnosis and Assessment of severity of confirmed Dengue infections in Vietnamese children: Is the WHO classification system helpful? Am. J. Trop. Med Hyg.2004; 70(2): 172-179. Seliati TE, et al. Dengue disease severity in Indonesian children: an evaluation of the WHO Classification system. BMC Infectious Disease 2007, 7:22 Bandyopadhyay S, Lum LC, Kroeger A. Classifying dengue: a review of the difficuties in using the WHO case classification for dengue hemorrhagic fever. Tropical Medicine and International Health Volume Il No. 8 pp 1238-1255 August 2006. ‘Alexander N, Balmaseda A, Coelho IC, Dimaano E, Hien TT, et al and the DENCO Study Group. Multicentre prospective study on dengue classification in four South-east Asian and three Latin ‘American countries. Trop Med Int Health. 2011: 16(8): 936-948, Basuki PS, Budiyanto1, Puspitasari D, Husada D, Darmowandowo W, Ismoedijantot, Soegijanto S, Yamanaka A. Application Of Revised Dengue Classification Criteria As A Severity Marker Of Dengue Viral Infection In Indonesia, Southeast Asian J Trop Med Public Health 2010; 41(6): 1088- 1094, Bamiol J, Gaczkowski R, Vega Barbato E, V da Cunha R, Salgado D, Martinez E, et al. Usefulness. and applicability of the revised dengue case classification by disease: multicentre study in 18 countries. BMC Infectious Diseases 2011, 11:106. http:/www.biomedcentral,com/1471- 2334/11/106, Narvaez F, Gutierrez G, Perez MA, Elizondo D, Nunez A, Balmaseda A, Hanis E. Evaluation of the Traditional and Revised WHO Classifications of Dengue Disease Severity. PLOS Neglected Tropical Disease 2011; 5(11): €1397. doi:10.137 ‘journal. pntd.0001397 Halstead SB. Paediatrics and Intemational Child Health 2012; 32(NO. S1): 5-8. Ludan A (Contributor). Chapter 41: Pediatric Fluid and Electrolyte Therapy. In Textbook of Pediatrics and Child Health. del Mundo F, Estrada FA, Santos-Ocampo PD, Navarro XR, editors, Manila: JMC Press. Fourth edition. 2000:1485-1499,16 17. 18, 19. 20. 21 22, 23, Holliday MA, Segar WE. Maintenance need for water in parenteral fluid therapy. Pediatrics 1957; 19:823. Greenbaum LA. “Deficit Therapy.” In Nelson Textbook of Pediatrics 19" ed. Klugman RM, Stanton BF, ST. Geme lll, Schor NF, Behrman RE, editors. Philadelphia: Elsevier Saunders; pp 245-249 | Jalac SLR, de Vera MJB, Alejandria M. The use of colloids and crystalloids in pediatric dengue ‘shock: a meta-analysis. Phil, J Microbiol Inf Dis 2010 Jan-June; 39(1): 14-27. Dung NM, Day NPJ, Tam DTH, et al: Fluid Replacement in DSS: A randomized, double blind comparison of four intravenous-fluid regimens. Clinical Infectious Disease: 1999; 29; 787- 94. Nhan Ngo Thi, Phuong CXT, Wills B, et al. Acute management of DSS: A randomized double blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis 2001;32:204-213. Wills BA, DungN, Loan, et al. Comparison of three fluid solutions for resuscitation in dengue shock ‘syndrome. NEJM Sept 2005; 353 No 9: 877-889, The 1998 National Working Group Consensus on the Treatment of DHF (Department of Health). 36” Bethesda Conference: Eligibility Recommendation for Athletes with Cardiovascular ‘Abnormalities. JACC;45 :8, pp1313-1375.Appendix A Calculation of Fluids in Obese or Overweight Patients” For obese and overweight patients, use the ideal body weight for calculation of fluid infusion: Estimated body | Normal maintenance | Fluid regimen based | Regimen based on weight, or IBW (kg) | fluid {mlmhour] based | on 2-3 ml/kg/hour 1.8-2mU/hour on Holliday-Segar (mi/hour) (mi/hour) formula 5 10 10-15 10 20 20-30 15 20. 20-45 20. 60. 40-60 25. 65. 50-75 20. 70. 60-80 35. 75. 70-105 40. ED 20-120 50. 20. 100-150 60. 700 90-120 70. 110 105-140 20. 120 120-150 Estimated Ideal Body Weight for Overweight or Obese Adults Height (em) Estimated, IBW (kg) for adult | Estimated IBW (ka) for adult males females 750 50 455 160 37 82. 170 6 615 180 75 70Appendix B Causes of fluid overload *° Excessive and/or too rapid intravenous fluids Incorrect use of hypotonic rather than isotonic crystalloid solution Inappropriate use of large volumes of intravenous fluids in patients with unrecognized severe bleeding Inappropriate transfusion of fresh-frozen plasma, platelet concentrates and cryoprecipitates Continuation of intravenous fluids after plasma leakage has resolved [24-48 hours from defervescence] Co-morbid conditions such as congenital or ischemic heart disease, chronic lung disease and renal disease Early clinical features of fluid overload? Puffy eyelids Distended abdomen (ascites) Tachypnea Mild dyspnea Late clinical features of fluid overload? Respiratory distress, difficulty in breathing Rapid breathing Chest wall indrawing Wheezing rather than crepitant rales Large pleural effusions Tense ascites Increased jugular pressure Hypertension‘Appendix C ‘Sample Monitoring Sheet for Dengue Patients Time and Date Parameters ‘Sensorium Cdearand | Odearand | Qclearand | Odearand | O-cearand lucia ludid lucie lucid lucid Orestless/ | Grestiess/ | Orestiess/ | Orestless/ | Orestiess/ combative | combative | combative | combative | combative Body temperature Fait rate Blood pressure Respiratory rate Pulse good good C good T good T good pressurelvolume | weak and | weak and | Qweakand | Qweak and | O weak and thread thread thread thread thread feeble or | Oiesbleor | feeble or |G feeble or | O feeble or absent absent absent absent absent Capilaryrefiltime | O=2sec | Dedsec | Dedeec | Gezses | Oe sec G>2sec | O>2sec | Gr2sec | G>2sec © — | O>2 sec Temperature warm ‘warm ‘warm warm Gwar of extremities Dold Dold Dold Dold Dold ‘Abdominal pain Vomiting Bleeding TWF infusion rate Urine Output 77 | Revsedberge Gases coe 707 EAMEMBERS OF THE TECHNICAL WORKING GROUP ON THE 2012 PPS REVISED GUIDELINES ON FLUID MANAGEMENT OF DF/DHF Overall Chair and Chair, Committee on Dengue: Ma. Liza Antoinette M. Gonzales, MD (Pediatric Infectious Disease) Co-Chair, Committee on Dengue: Maria Anna P. Banez, MD (Pediatric Infectious Disease) Members: Ma, Louisa U. Peralta, MD (Pediatric ICU) Benjamin T. Lim, MD (Pediatric ICU) Anita G, Marasigan, MD (Pec teu) Ma. Norma V. Zamora, MD (Pediatric Nephrology) Cynthia A. Aguirre, MD (Pediatric Infectious Disease) Gyneth Lourdes G. Bibera, MD (Pediatric Infectious Disease) Rosario Z. Capeding, MD (Pediatric Infectious Disease) Reynaldo C. De Castro, Jr., MD (Pediatric Hematology) Flerida G. Hernandez, MD (Pediatric Hematology) Dr. Magdalena Lagamayo, MD (Pediatric Cardiology) Anna Lisa T. Ong-Lim, MD (Pediatric Infectious Disease) Revised 01 October 2012