Fluid Management in Dengue Fever and Dengue Haemorrhagic Fever

Fluid Management in Dengue Fever and Dengue Haemorrhagic Fever Dengue infection Dr. A LakKumar Fernando, Consultant Paediatrician Dengue is a disease which is silently transmitted in the community. For instance out of 10,000 who are infected with the dengue virus, only about 1,000 patients will be symptomatic. Out of that half will have only a non specific self limiting viral syndrome. Out of the other half the majority will have dengue fever (DF) and only about 1/5 th will have dengue haemorrhagic fever (DHF). The essential feature in DHF is the plasma leak. Out of all DHF patients, only 1-2 % will have Dengue Shock Syndrome (DSS). Rarely some DHF patients will have unusual complications like prolonged shock, liver failure, encephalopathy, renal failure or co-infections. A good understanding of the disease process will help proper management that will lead to lower morbidity and mortality. Dengue infection is a dynamic disease. Its clinical course changes as the disease progresses. After the incubation period the illness begins abruptly with fever. DF vs DHF When a patient presents with Dengue or dengue like illness the differentiation between DHF and DF will be a key factor in guiding the management. DF and DHF are two different clinical conditions from the beginning. They look very similar in the first two days. However badly managed DF will never become DHF. 1

Dengue fever In dengue fever there is no plasma leakage. In about 50% of patients the platelet count may drop even below 100,000. Leucopenia (WBC <5,000) is seen in DF too like in DHF. Headache, muscle/ joint/ bone pain, erythematous or macula-papular rash, positive tourniquet test, skin heamorrhages are seen sometimes more in DF than in DHF. Haemorrhagic manifestations of DF include petichiae, purpura, gum or nasal bleeding, gastrointestinal bleeding, haematuria, and menorrhagia. Haemorrhagic manifestations are not enough to call the disease DHF. Dengue haemorrhagic fever The diagnosis of DHF will depend on objective evidence of leaky capillaries. The other criteria include fever or recent history of acute fever, haemorrhagic manifestations, and low platelet counts ( 100,000/ml). Positive tourniquet test is a feature in both DF and DHF. DHF is a dynamic disease. It has three important phases: FEBRILE, CRITICAL and RECOVERY phase. Clinical Case Definition for DHF 4 Necessary Criteria:(all four needed) Fever, or recent history of acute fever Hemorrhagic manifestations Low platelet count (100,000/mm3 or less) Objective evidence of leaky capillaries: Elevated hematocrit (20% or more over baseline) Low albumin Pleural or other effusions Febrile phase There is sudden onset high grade fever that lasts 2 to 7 days. There can be facial puffing, skin erythema, myalgia, arthralgia and headache. Some patients may have sore throat, injected pharynx, and conjunctival injection. Anorexia, nausea and vomiting are common. These features are indistinguishable between DF and DHF. Presence of tender hepatomegaly favours a diagnosis of DHF. Critical phase The critical phase occurs towards the late febrile phase (often after the 3 rd day) and lasts about for 24 to 48 hours. It is very rare in the first two days, usually occur between the 4 th to 5 th day but may sometimes go up to the 7 th day. Rapid drop in temperature may occur as the patient enters the critical phase. In other viral infections as the fever subsides the patient s condition improves, but in dengue if there is no or minimal plasma leak the patient will become better but will get worse if critical volume of plasma is lost. Rising haematocrit 20% confirms such plasma leak. The 20% is calculated by taking into consideration the baseline haematocrit (Hct).(A recent full blood count will help identify the baseline haematocrit). For example if the initial Hct is 35%, a 3.5% increase of Hct (38.5%) will indicate a 10% increase of Hct, and the increase of Hct upto 42% indicates 20% increase. The venous Hct is 2% higher than capillary Hct in non shock patients. In shock patients the capillary Hct is higer. Other evidence of plasma leak such as pleural effusions and ascitis will also help to identify the critical phase of DHF. 2

In a few patients evidence of plasma leaking may not be very clear. Serum cholesterol and serum albumin could also be helpful in such situations. Albumin and cholesterol will accompany plasma out of the circulation during leaking. A reduction in the baseline (non fasting) S. Cholesterol and/ or albumin during the illness can suggest the patient to be in the leaking phase. S. Albumin of <3.5g/dl and cholesterol of <100mg/dl should raise suspicion that the patient could be in the leaking phase. (Population standards of the values are perhaps needed for best interpretation) The critical phase lasts only 24 to 48 hours. This is the most important part of case management. Mortality, morbidity and almost all complications are related to the patient management during this phase. Prolonged shock and fluid overload are the major causes of death, organ failure or DIC in most patients with dengue. Careful fluid management during the critical phase could very significantly improve the final outcome. During this phase the patient needs to be reviewed very frequently several times a day. Recovery phase (convalescent phase) Usually lasts 3-5 days, could be longer in adults. Here the plasma leak stops and fluid is reabsorbed. General well being and appetite improve. Patient s haemodynamic status stabilizes and diruresis begins. Some patients will have classical recovery rash which typically has white areas in a red background. Some may have generalized itching. The recovery of platelet count is typically preceded by the recovery of white cell count. Fluid Management in Dengue Fluid calculation per body weight The first two days: Dengue shock is extremely rare in the first two days and patients are generally not expected to be in the critical phase during this period. In the first two days patient have to be hydrated adequately correcting the losses. If there is fever and vomiting, total IV + oral fluids equal to maintenance (M) + 5% (5% of body weight=50ml/kg) could be given during each 24 hour period. If there is no such loss, the fluid requirement for this period is the normal maintenance. Calculation of Ideal Body Weight Best Method: Weight for height using a growth chart Weigh for age using a growth chart In an emergency situation use these formulae <1 year Age (in Months)+ 9 2 < 7 years (Age x 2)+ 8 > 7 years Age x 3 APLS (Age + 4) x 2 3

After the 3 rd day, if the patient has DHF he can start leaking fluid at any time. Unlike in the first two days of non leak it is not advisable to promote large amounts of fluids to be taken freely during this period as it may lead to fluid overload. Some fluid restriction is useful during the critical 24 to 48 hours and even oral fluids can cause fluid overload. The total amount of fluid recommended during the entire critical phase is only M + 5% deficit (M + 50ml/kg). This total fluid amount could be spread over a 48 hour period if fluid therapy is initiated when the patient is leaking but in no shock. During the critical 48 hours fluids start leaking and gradually the leaking increases reaching a peak around 24hours. After 24 hours the leaking starts slowing down again and will stop after a further 24 hours making the total amount of leaking (=critical phase) to 48 hours. The total fluid replacement needed for the entire leaking phase is only one quota of M + 5%. If the patient had been in hospital from the beginning it is important to identify the exact timing of the onset of leaking. This is important as the leaking is almost certainly expected to stop after about 48 hours from this onset. Initially when pulse and blood pressure are stable fluids could be given both orally and IV (amount to be determined by ability to drink etc. ) keeping in mind the total fluid quota available for 48 hour period. Oral fluids has to be electrolyte solutions and not plain water. Large quantities of fluid liberally is not recommended and maintenance of a urine output of 0.5-1 ml/ kg/hour indicates the amount of fluid given is adequate. It is also essential that all patients in the critical phase are on IV fluids (Normal saline or Hartmann s and in the very young N/2 + 5% dextrose) even in minimal amounts (0.5-1.5 ml/kg) even though they are haemodynamically stable. DHF is a very dynamic disease where haemodynamic state can change very rapidly to profound shock and death. It is important to monitor such patients very frequently specially towards the peak of leaking with readiness to immediate fluid resuscitation. Since rapid leaking making a patient going in to shock within a short period is not always predictable, it is prudent to keep all DHF patients in critical phase on minimal IV fluids so that whenever shock is detected what is needed is to rapidly increase the rate of infusion. Until the very last stage of shock a patient can appear conscious and very alert and if pulse, BP are not measured early shock could be missed. The patient will develop restlessness briefly before becoming pulseless and frequent monitoring and readiness for resuscitation can save life at this stage. As the leaking gradually increases the amount of fluid needed will also go up. The amount of fluid needed for maintenance could go even up to 7ml/kg/h or more, but would unlikely to stay at the same level as leaking will start slowing down towards the end of the critical stage. Keeping maintenance fluid at a higher rate without monitoring can lead to fluid overload. If fluid is restricted by keeping in mind the total fluid quota available (M+5%) fluid overload could be avoided. If a higher maintenance is unable to maintain the pulse pressure, fluid boluses should be used. If a patient presents with shock (cold clammy skin, pulse BP unrecordable) one would assume that the patient had continued to leak before coming to hospital. As the peak of leaking occur around 24 hours, a patient who has gone in to significant shock will be in a stage of leaking that has passed about 24 hours and will only have about further 24 hours before the leaking stops. In such patients the total fluid quota of M+ 5% could be given over the next 24 hours (not 48 hours) and this will include the fluid given for resuscitation. While resuscitating a patient with shock, the initial bolus could be 20ml/kg as fast as possible or free flow of IV fluids. But the moment pulse and blood pressure become recordable the rate has to be reduced and boluses after this should be 10ml/kg/h. 4

Depending on the haemodynamic status the rate of fluids could be decided. As the patient enters the critical phase the initial leaking will be slow. A rate of 1.5ml /kg/h (oral + IV) is sufficient as the initial rate. This rate could be increased and decreased according to the rate of leaking over the next 48 hours, keeping in mind the total fluid quota. Shock usually occurs at the peak of leaking and leaking has already occurred for several hours before the patient goes into shock. In shock the highest rate of infusion will be at the time of resuscitation. And the rate will then gradually come down as the leaking slows down over the next 24 hours. 5

Fluid boluses in the critical phase Normal Saline: 10ml/kg/hour initially when there is no fluid overload. If there is inadequate response to one bolus a second bolus could be given before switching over to dextran or starch. When normal saline is given it remains in circulation only for about 1 to 2 hours or less during leaking. Even fluids like fresh frozen plasma (FFP) will readily leak and will not hold blood pressure for long periods. A colloid (dextran or starch) will remain in circulation for a longer period (4-6 hours). For example in a patient who has already received a significant quantity of fluid quota has several more hours to complete the leaking phase, by using a colloid one could save the fluid quantity needed to maintain pulse and BP. For initial resuscitation normal saline is probably the best solution but other fluids like FFP, Gelafundin, haemaccel could also be used. Dextran is not the best resuscitation fluid as its hyperosmolar, high molecular weight properties may not open microcirculation. Both dextran and 6% hetastarch are the most commonly used colloids helpful in patients with difficulty in maintaining pulse and blood pressure when there is a fluid overload. Being large molecular weight colloids, they are capable of remaining in the circulation or expanding volume (specially Dextran 40) for a longer period. One could use up to 3 doses of Dextran 40 (each as 10ml/kg/hour) during a 24 hour period (6 doses within 48 hours). 6% hetastarch could be given upto 5 doses (each as 10ml/kg/hour) per 24 hours (10 doses within 48 hours). Both hetastarch and dextran 40 are only recommended during the critical phase (24 to 48h) of DHF. They should only be used as boluses (10ml/kg/h) and not as infusions unlike saline. About 60% of patients with dengue shock can be managed only with normal saline without using a colloid. Patients with severe shock and fluid overload will need colloids. Soon after a fluid bolus (either crystalloid or colloid) given over a maximum of one hour, change the IV fluids as crystalloids for maintenance. Then it is best to try and reduce the infusion rate to prevent overload. If at a lower infusion rate BP, pulse is not sustainable another bolus will be needed. If there are many hours to go with limited fluid quota left, use a colloid for the bolus. If there is only little time left and there is enough fluid quota left a crystalloid bolus can help and colloids will be unnecessary. When colloids such as starch are used it is important to keep in mind issues like hypersensitivity / allergy (for certain preparations of starch). It is important to avoid an unexpected situation like an anaphylactic shock on top of a dengue shock. Since the critical phase is a very dynamic phase it is important to monitor the patient frequently during this phase. Monitoring should include pulse, BP, capillary refill time, warmth/ coldness of peripheries, respiratory rate and spo 2. When the patient is in shock these signs should be monitored every 15 to 30 mins, and then 1-2 hourly when the patient is stable. Regular Hct measurement is also important during critical phase. As leaking progresses the Hct will go up. When the Hct come down the patient should become more stable haemodynamically and should improve. While in the critical phase if patient deteriorates while the Hct improve (while Hct drops) one has to suspect bleeding. During the initial phase of very slow leaking if two large fluid boluses are given or higher infusion rates are used the drop in Hct will be too high. As the patient reaches the end of critical phase, the rate of leaking slows down. At this stage even when the Hct is high giving more fluid to bring down the Hct is not recommended. For example if Hct is 52% and the patient has only very few hours to complete the critical phase there is no necessity in giving fluid to bring down the Hct. When leaking stops fluid will start reabsorbing and the high Hct will then come 6

down. Any fluid given just before this will only facilitate circulatory overload and heart failure. Identifying the beginning of the critical phase and predicting the end is a key factor in guiding fluid therapy. The above fluid management is applicable to most patients who enters the critical phase in dengue. Fluid management of patients with complications will be dealt in another document. - Dr A. LakKumar Fernando. MBBS, DCH, MD(Paed), MRCPCH(UK), FRCP(Lond), is a Consultant Paediatrician at DGH Gampaha. The above article is based on the training he received at the WHO Collaborating Centre for Case Management of Dengue/DHF/DSS at Queen Sirikit National Institute of Child Health Bangkok, Thailand in May 2010. 7