DENGUE:TypesThere are two main types of volume expanders; crystalloids and colloids. Crystalloids are aqueoussolutions of mineral salts or other water-soluble molecules. Colloids contain larger insoluble molecules,such as gelatin; blood itself is a colloid. ColloidsColloids preserve a high colloid osmotic pressure in the blood, while, on the other hand, this parameteris decreased by crystalloids due to hemodilution. Therefore, they should theoretically preferentiallyincrease the intravascular volume, whereas crystalloids also increase the interstitial volume andintracellular volume. However, there is still controversy as to the actual difference in efficacy due to thisdifference in action. Another difference is that crystalloids generally are much cheaper thancolloids. Hydroxyethyl starchMain article: Hydroxyethyl starchHydroxyethyl starch (HES/HAES, common trade names: Hespan, Voluven) is one of the most frequentlyused colloids. An intravenous solution of hydroxyethyl starch is used to prevent shock following severeblood loss caused by trauma, surgery, or some other problem. It increases the blood volume, allowingred blood cells to continue to deliver oxygen to the body. CrystalloidsThe most commonly used crystalloid fluid is normal saline, a solution of sodium chloride at 0.9%concentration, which is close to the concentration in the blood (isotonic). Ringers lactate or Ringersacetate is another isotonic solution often used for large-volume fluid replacement. A solution of 5%dextrose in water, sometimes called D5W, is often used instead if the patient is at risk for having lowblood sugar or high sodium. The choice of fluids may also depend on the chemical properties of themedications being given.Intravenous fluids must always be sterile.
 Ringers solutionLactated Ringers solution contains 28 mmol/L lactate, 4 mmol/L K+ and 1.5 mmol/L Ca2+. It is verysimilar - though not identical to - Hartmanns Solution, the ionic concentrations of which differ.Ringers acetate consists of 28 mmol/L acetate, 4 mmol/L K+ and 1.5 mmol/L Ca2+.Normal salineMain article: Saline (medicine)Normal saline (NS) is the commonly-used term for a solution of 0.91% w/v of NaCl, about 300mOsm/L. Less commonly, this solution is referred to as physiological saline or isotonic saline, neitherof which is technically accurate. NS is used frequently in intravenous drips (IVs) for patients who cannottake fluids orally and have developed or are in danger of developing dehydration or hypovolemia. NS istypically the first fluid used when hypovolemia is severe enough to threaten the adequacy of bloodcirculation, and has long been believed to be the safest fluid to give quickly in large volumes. However, itis now known that rapid infusion of NS can cause metabolic acidosis. Glucose (dextrose)Intravenous sugar solutions, such as with glucose (also called dextrose), have the advantage of providingsome energy, and may thereby provide the entire or part of the energy component of parenteralnutrition.Types of glucose/dextrose include: D5W (5% dextrose in water), which consists of 278 mmol/L dextrose D5NS (5% dextrose in normal saline), which, in addition, contains normal saline.
 Comparison tableComposition of common crystalloid solutions Solution Other Name[Na+](mmol/L) [Cl-](mmol/L) [Glucose](mmol/L) [Glucose](mg/dl)D5W 5% Dextrose 0 0 278 50002/3D & 1/3S 3.3% Dextrose / 0.3% saline 51 51 185 3333Half-normal saline 0.45% NaCl 77 77 0 0Normal saline 0.9% NaCl 154 154 0 0Ringers lactate Lactated Ringer 130 109 0 0D5NS 5% Dextrose, Normal Saline 154 154 278 5000Effect of adding one litre SolutionChange in ECF Change in ICFD5W 333 mL 667 mL2/3D & 1/3S 556 mL 444 mLHalf-normal saline 667 mL 333 mLNormal saline 1000 mL 0 mLRingers lactate 900 mL 100 mLSupportive:Patients require emergency treatment and urgent referral when they are in the criticalphase of disease, i.e. when they have:– severe plasma leakage leading to dengue shock and/or fluid accumulation
with respiratory distress;– severehaemorrhages;– severe organ impairment (hepatic damage, renal impairment, cardiomyopathy,encephalopathy or encephalitis).All patients with severe dengue should be admitted to a hospital with access tointensive care facilities and blood transfusion. Judicious intravenous fluid resuscitationis the essential and usually sole intervention required. The crystalloid solution shouldbe isotonic and the volume just sufficient to maintain an effective circulation during theperiod of plasma leakage. Plasma losses should be replaced immediately and rapidlywith isotonic crystalloid solution or, in the case of hypotensive shock, colloid solutions(Textbox M). If possible, obtain haematocrit levels before and after fluid resuscitation.There should be continued replacement of further plasma losses to maintain effectivecirculation for 24–48 hours.Blood transfusion should be given only in cases with suspected/severe bleeding.Treatment of shockThe action plan for treating patients with compensated shock is as follows (Textboxes Dand N, Figure 2.2):Start intravenous fluid resuscitation with isotonic crystalloid solutions at 5–10 ml/kg/hour over onehour. Then reassess the patient’s condition (vital signs, capillary refill time, haematocrit, urine output).The next steps depend on the situation.• If the patient’s condition improves, intravenous fluids should be gradually reduced to 5–7 ml/kg/hr for1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, then to 2–3 ml/kg/hr, and then further depending onhaemodynamicstatus, which can be maintained for up to 24–48 hours. (See textboxes H and J for a moreappropriate estimate of the normal maintenance requirement based on ideal body weight).
• If vital signs are still unstable (i.e. shock persists), check the haematocrit after the first bolus. If thehaematocrit increases or is still high (>50%), repeat a second bolus of crystalloid solution at 10–20ml/kg/hr for one hour. After this second bolus, if there is improvement, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, and then continue to reduce as above. If haematocritdecreases compared to theinitial reference haematocrit (<40% in children and adult females, <45% in adult males), this indicatesbleeding and the need to cross-match and transfuse blood as soon as possible (see treatment forhaemorrhagic complications).• Further boluses of crystalloid or colloidal solutions may need to be given during the next 24–48 hours.A decrease in haematocrit together with unstable vital signs (particularly narrowing of the pulsepressure, tachycardia, metabolic acidosis, poor urine output) indicates major haemorrhage and the needfor urgent blood transfusion. Yet a decrease in haematocrittogether with stable haemodynamic statusand adequate urine output indicates haemodilution and/or reabsorption of extravasated fluids, so inthis case intravenous fluids must be discontinued immediately to avoid pulmonary oedema.Treatment of haemorrhagic complicationsMucosal bleeding may occur in any patient with dengue but, if the patient remains stable with fluidresuscitation/replacement, it should be considered as minor. The bleeding usually improves rapidlyduring the recovery phase. In patients with profound thrombocytopaenia, ensure strict bed rest andprotect from trauma to reduce the risk of bleeding. Do not give intramuscular injections to avoidhaematoma. It should be noted that prophylactic platelet transfusions for severethrombocytopaenia inotherwise haemodynamically stable patients have not been shown to be effective and are not necessarySevere bleeding can be recognized by: – persistent and/or severe overt bleeding in the presence ofunstable haemodynamic status, regardless of the haematocrit level;– a decrease in haematocrit after fluid resuscitation together with unstable haemodynamic status;– refractory shock that fails to respond to consecutive fluid resuscitation of 40-60 ml/kg;– hypotensive shock with low/normal haematocrit before fluid resuscitation;– persistent or worsening metabolic acidosis ± a well-maintained systolic bloodpressure, especially in those with severe abdominal tenderness and distension.
Consider repeating the blood transfusion if there is further blood loss or no appropriate rise inhaematocrit after blood transfusion. There is little evidence to support the practice of transfusingplatelet concentrates and/or fresh-frozen plasma for severe bleeding. It is being practised when massivebleeding can notbe managed with just fresh whole blood/fresh-packed cells, but it may exacerbate thefluid overload.Causes of fluid overload are:– excessive and/or too rapid intravenous fluids;– incorrect use of hypotonic rather than isotonic crystalloid solutions;– inappropriate use of large volumes of intravenous fluids in patients with unrecognized severebleeding;– inappropriate transfusion of fresh-frozen plasma, platelet concentrates and cryoprecipitates;– continuation of intravenous fluids after plasma leakage has resolved (24–48 hours fromdefervescence);– co-morbid conditions such as congenital or ischaemic heart disease, chronic lung and renal diseases.Early clinical features of fluid overload are:– respiratory distress, difficulty in breathing;– rapid breathing;– chest wall in-drawing;– wheezing (rather than crepitations);– large pleural effusions;– tense ascites;– increased jugular venous pressure (JVP).Late clinical features are:– pulmonaryoedema (cough with pink or frothy sputum ± crepitations, cyanosis);– irreversible shock (heart failure, often in combination with ongoinghypovolaemia).
Patients who remain in shock with low or normal haematocrit levels but show signs of fluid overloadmay have occult haemorrhage. Further infusion of large volumes of intravenous fluids will lead only to apoor outcome.Other complications of dengueBoth hyperglycaemia and hypoglycaemia may occur, even in the absence of diabetes mellitus and/orhypoglycaemic agents. Electrolyte and acid-base imbalances are also common observations in severedengue and are probably related to gastrointestinal losses through vomiting and diarrhoea or to the useof hypotonic solutions for resuscitation and correction of dehydration. Hyponatraemia, hypokalaemia,hyperkalaemia, serum calcium imbalances and metabolic acidosis (sodium bicarbonate for metabolicacidosis is not recommended for pH ≥ 7.15) can occur. One should also be alert for co-infectionsandnosocomial infections.Choice of intravenous fluids for resuscitationBased on the three randomized controlled trials comparing the different types of fluid resuscitationregime indengue shock in children, there is no clear advantage to the use of colloids over crystalloids in terms ofthe overalloutcome. However, colloids may be the preferred choice if the blood pressure has to be restoredurgently, i.e. inthose with pulse pressure less than 10 mm Hg. Colloids have been shown to restore the cardiac indexand reducethe level of haematocrit faster than crystalloids in patients with intractable shock (18–20).An ideal physiological fluid is one that resembles the extracellular and intracellular fluids compartmentsclosely. However, the available fluids have their own limitations when used in large quantities.Therefore it is advisable to understand the limitations of these solutions to avoid their respectivecomplications.Crystalloids0.9% saline (“normal” saline)Normal plasma chloride ranges from 95 to 105 mmol/L. 0.9% Saline is a suitable option for initial fluidresuscitation, but repeated large volumes of 0.9% saline may lead to hyperchloraemic acidosis.Hyperchloraemicacidosis may aggravate or be confused with lactic acidosis from prolonged shock.Monitoring the chlorideand lactate levels will help to identify this problem. When serum chloride levelexceeds the normal range, it isadvisable to change to other alternatives such as Ringer’s Lactate.
Ringer’s LactateRinger’s Lactate has lower sodium (131 mmol/L) and chloride (115 mmol/L) contents and an osmolalityof273 mOsm/L. It may not be suitable for resuscitation of patients with severehyponatremia. However,it is a suitable solution after 0.9 Saline has been given and the serum chloride level has exceeded thenormal range.Ringer’s Lactate should probably be avoided in liver failure and in patients takingmetformin where lactate metabolism may be impaired.ColloidsThe types of colloids are gelatin-based, dextran-based and starch-based solutions. One of the biggestconcerns regarding their use is their impact on coagulation. Theoretically, dextrans bind to vonWillebrand factor/Factor VIII complex and impair coagulation the most. However, this was not observedto have clinical significance in fluid resuscitation in dengue shock. Of all the colloids, gelatine has theleast effect on coagulation but the highest risk of allergic reactions. Allergic reactions such as fever, chillsand rigors have also been observed in Dextran 70. Dextran 40 can potentially cause an osmotic renalinjury in hypovolaemic patients.