2.1.1. Febrile phase

Patients typically develop high-grade fever suddenly. This acute febrile phase usually lasts 2–7 days and is often accompanied by facial flushing, skin erythema, generalized body ache, myalgia, arthralgia and headache (1). Some patients may have sore throat, injected pharynx and conjunctival injection. Anorexia, nausea and vomiting are common. It can be difficult to distinguish dengue clinically from non-dengue febrile diseases in the early febrile phase. A positive tourniquet test in this phase increases the probability of dengue (3,4). In addition, these clinical features are indistinguishable between severe and non-severe dengue cases. Therefore monitoring for warning signs and other clinical parameters (Textbox C) is crucial to recognizing progression to the critical phase.

Textbox C

Warning signs.

Mild haemorrhagic manifestations like petechiae and mucosal membrane bleeding (e.g. nose and gums) may be seen (3,5). Massive vaginal bleeding (in women of childbearing age) and gastrointestinal bleeding may occur during this phase but is not common (5). The liver is often enlarged and tender after a few days of fever (3). The earliest abnormality in the full blood count is a progressive decrease in total white cell count, which should alert the physician to a high probability of dengue.

2.1.2. Critical phase

Around the time of defervescence, when the temperature drops to 37.5–38°C or less and remains below this level, usually on days 3–7 of illness, an increase in capillary permeability in parallel with increasing haematocrit levels may occur (6,7). This marks the beginning of the critical phase. The period of clinically significant plasma leakage usually lasts 24–48 hours.

Progressive leukopenia (3) followed by a rapid decrease in platelet count usually precedes plasma leakage. At this point patients without an increase in capillary permeability will improve, while those with increased capillary permeability may become worse as a result of lost plasma volume. The degree of plasma leakage varies. Pleural effusion and ascites may be clinically detectable depending on the degree of plasma leakage and the volume of fluid therapy. Hence chest x-ray and abdominal ultrasound can be useful tools for diagnosis. The degree of increase above the baseline haematocrit often reflects the severity of plasma leakage.

Shock occurs when a critical volume of plasma is lost through leakage. It is often preceded by warning signs. The body temperature may be subnormal when shock occurs. With prolonged shock, the consequent organ hypoperfusion results in progressive organ impairment, metabolic acidosis and disseminated intravascular coagulation. This in turn leads to severe haemorrhage causing the haematocrit to decrease in severe shock. Instead of the leukopenia usually seen during this phase of dengue, the total white cell count may increase in patients with severe bleeding. In addition, severe organ impairment such as severe hepatitis, encephalitis or myocarditis and/or severe bleeding may also develop without obvious plasma leakage or shock (8).

Those who improve after defervescence are said to have non-severe dengue. Some patients progress to the critical phase of plasma leakage without defervescence and, in these patients, changes in the full blood count should be used to guide the onset of the critical phase and plasma leakage.

Those who deteriorate will manifest with warning signs. This is called dengue with warning signs (Textbox C). Cases of dengue with warning signs will probably recover with early intravenous rehydration. Some cases will deteriorate to severe dengue (see below).

2.1.3. Recovery phase

If the patient survives the 24–48 hour critical phase, a gradual reabsorption of extravascular compartment fluid takes place in the following 48–72 hours. General well-being improves, appetite returns, gastrointestinal symptoms abate, haemodynamic status stabilizes and diuresis ensues. Some patients may have a rash of “isles of white in the sea of red” (9). Some may experience generalized pruritus. Bradycardia and electrocardiographic changes are common during this stage.

The haematocrit stabilizes or may be lower due to the dilutional effect of reabsorbed fluid. White blood cell count usually starts to rise soon after defervescence but the recovery of platelet count is typically later than that of white blood cell count.

Respiratory distress from massive pleural effusion and ascites will occur at any time if excessive intravenous fluids have been administered. During the critical and/or recovery phases, excessive fluid therapy is associated with pulmonary oedema or congestive heart failure.

The various clinical problems during the different phases of dengue can be summarized as in Table 2.1.

Table 2.1

Febrile, critical and recovery phases in dengue.

2.1.4. Severe dengue

Severe dengue is defined by one or more of the following: (i) plasma leakage that may lead to shock (dengue shock) and/or fluid accumulation, with or without respiratory distress, and/or (ii) severe bleeding, and/or (iii) severe organ impairment.

As dengue vascular permeability progresses, hypovolaemia worsens and results in shock. It usually takes place around defervescence, usually on day 4 or 5 (range days 3–7) of illness, preceded by the warning signs. During the initial stage of shock, the compensatory mechanism which maintains a normal systolic blood pressure also produces tachycardia and peripheral vasoconstriction with reduced skin perfusion, resulting in cold extremities and delayed capillary refill time. Uniquely, the diastolic pressure rises towards the systolic pressure and the pulse pressure narrows as the peripheral vascular resistance increases. Patients in dengue shock often remain conscious and lucid. The inexperienced physician may measure a normal systolic pressure and misjudge the critical state of the patient. Finally, there is decompensation and both pressures disappear abruptly. Prolonged hypotensive shock and hypoxia may lead to multi-organ failure and an extremely difficult clinical course (Textbox D).

Textbox D

Haemodynamic assessment: continuum of haemodynamic changes.

The patient is considered to have shock if the pulse pressure (i.e. the difference between the systolic and diastolic pressures) is ≤ 20 mm Hg in children or he/she has signs of poor capillary perfusion (cold extremities, delayed capillary refill, or rapid pulse rate). In adults, the pulse pressure of ≤ 20 mm Hg may indicate a more severe shock. Hypotension is usually associated with prolonged shock which is often complicated by major bleeding.

Patients with severe dengue may have coagulation abnormalities, but these are usually not sufficient to cause major bleeding. When major bleeding does occur, it is almost always associated with profound shock since this, in combination with thrombocytopaenia, hypoxia and acidosis, can lead to multiple organ failure and advanced disseminated intravascular coagulation. Massive bleeding may occur without prolonged shock in instances when acetylsalicylic acid (aspirin), ibuprofen or corticosteroids have been taken.

Unusual manifestations, including acute liver failure and encephalopathy, may be present, even in the absence of severe plasma leakage or shock. Cardiomyopathy and encephalitis are also reported in a few dengue cases. However, most deaths from dengue occur in patients with profound shock, particularly if the situation is complicated by fluid overload.

Severe dengue should be considered if the patient is from an area of dengue risk presenting with fever of 2–7 days plus any of the following features:

• There is evidence of plasma leakage, such as:

  –

  high or progressively rising haematocrit;

  –

  pleural effusions or ascites;

  –

  circulatory compromise or shock (tachycardia, cold and clammy extremities, capillary refill time greater than three seconds, weak or undetectable pulse, narrow pulse pressure or, in late shock, unrecordable blood pressure).

• There is significant bleeding.
• There is an altered level of consciousness (lethargy or restlessness, coma, convulsions).
• There is severe gastrointestinal involvement (persistent vomiting, increasing or intense abdominal pain, jaundice).
• There is severe organ impairment (acute liver failure, acute renal failure, encephalopathy or encephalitis, or other unusual manifestations, cardiomyopathy) or other unusual manifestations.

2.2.1. Introduction

Reducing dengue mortality requires an organized process that guarantees early recognition of the disease, and its management and referral when necessary. The key component of the process is the delivery of good clinical services at all levels of health care, from primary to tertiary levels. Most dengue patients recover without requiring hospital admission while some may progress to severe disease. Simple but effective triage principles and management decisions applied at the primary and secondary care levels, where patients are first seen and evaluated, can help in identifying those at risk of developing severe disease and needing hospital care. This should be complemented by prompt and appropriate management of severe dengue in referral centres.

Activities at the first level of care should focus on:

–

recognizing that the febrile patient could have dengue;

–

notifying early to the public health authorities that the patient is a suspected case of dengue;

–

managing patients in the early febrile phase of dengue;

–

recognizing the early stage of plasma leakage or critical phase and initiating fluid therapy;

–

recognizing patients with warning signs who need to be referred for admission and/or intravenous fluid therapy to a secondary health care facility;

–

recognizing and managing severe plasma leakage and shock, severe bleeding and severe organ impairment promptly and adequately.

2.2.2. Primary and secondary health care centres

At primary and secondary levels, health care facilities are responsible for emergency/ambulatory triage assessment and treatment.

Triage is the process of rapidly screening patients soon after their arrival in the hospital or health facility in order to identify those with severe dengue (who require immediate emergency treatment to avert death), those with warning signs (who should be given priority while waiting in the queue so that they can be assessed and treated without delay), and non-urgent cases (who have neither severe dengue nor warning signs).

During the early febrile phase, it is often not possible to predict clinically whether a patient with dengue will progress to severe disease. Various forms of severe manifestations may unfold only as the disease progresses through the critical phase, but the warning signs are good indicators of a higher risk of developing severe dengue. Therefore, the patient should have daily outpatient health care assessments for disease progression with careful checking for manifestations of severe dengue and warning signs.

Health care workers at the first levels of care should apply a stepwise approach, as suggested in Table 2.2.

Table 2.2

A stepwise approach to the management of dengue.

Section 2.3 gives treatment recommendations for the groups A–C.

2.2.3. Referral centres

Referral centres receiving severely ill dengue patients must be able to give prompt attention to referred cases. Beds should be made available to those patients who meet the admission criteria, even if elective cases have to be deferred. If possible, there should be a designated area to cohort dengue patients, and a high-dependency unit for closer monitoring of those with shock. These units should be staffed by doctors and nurses who are trained to recognize high-risk patients and to institute appropriate treatment and monitoring.

A number of criteria may be used to decide when to transfer a patient to a high-dependency unit. These include:

–

early presentation with shock (on days 2 or 3 of illness);

–

severe plasma leakage and/or shock;

–

undetectable pulse and blood pressure;

–

severe bleeding;

–

fluid overload;

–

organ impairment (such as hepatic damage, cardiomyopathy, encephalopathy, encephalitis and other unusual complications).

2.2.4. Resources needed

In the detection and management of dengue, a range of resources is needed to deliver good clinical services at all levels. Resources include (10):

• Human resources: The most important resource is trained doctors and nurses. Adequate health personnel should be allocated to the first level of care to help in triage and emergency management. If possible, dengue units staffed by experienced personnel could be set up at referral centres to receive referred cases, particularly during dengue outbreaks, when the number of personnel main need to be increased.
• Special area: A well equipped and well staffed area should be designated for giving immediate and transitory medical care to patients who require intravenous fluid therapy until they can be transferred to a ward or referral health facility.
• Laboratory resources: The most important laboratory investigation is that of serial haematocrit levels and full blood counts. These investigations should be easily accessible from the health centre. Results should be available within two hours in severe cases of dengue. If no proper laboratory services are available, the minimum standard is the point-of-care testing of haematocrit by capillary (finger prick) blood sample with the use of a microcentrifuge.
• Consumables: Intravenous fluids such as crystalloids, colloids and intravenous giving sets should be available.
• Drugs: There should be adequate stocks of antipyretics and oral rehydration salts. In severe cases, additional drugs are necessary (vitamin K1, Ca gluconate, NaHCO₃, glucose, furosemide, KCl solution, vasopressor, and inotropes).
• Communication: Facilities should be provided for easy communication, especially between secondary and tertiary levels of care and laboratories, including consultation by telephone.
• Blood bank: Blood and blood products will be required by only a small percentage of patients but should be made readily available to those who need them.

2.2.5. Education and training

To ensure the presence of adequate staffing at all levels, the education and training of doctors, nurses, auxiliary health care workers and laboratory staff are priorities. Educational programmes that are customized for different levels of health care and that reflect local capacity should be supported and implemented widely. The educational programmes should develop capacities for effective triage and should improve recognition, clinical management and laboratory diagnosis of dengue.

National committees should monitor and evaluate clinical management and outcomes. Review committees at different levels (e.g. national, state, district, hospital) should review all dengue deaths, and, if possible, all cases of severe dengue, evaluate the health care delivery system, and provide feedback to doctors on how to improve care.

In dengue-endemic countries, the knowledge of dengue, the vectors and transmission of disease should be incorporated into the school curriculum. The population should also be educated about dengue in order to empower patients and their families in their own care – so that they are prepared to seek medical care at the right time, avoid self-medication, identify skin bleedings, consider the day of defervescence (and during 48 hours) as the time when complications usually occur, and look for warning signs such as intense and continuous abdominal pain and frequent vomiting.

The mass media can give an important contribution if they are correctly briefed. Workshops and other meetings with journalists, editors, artists and executives can contribute to drawing up the best strategy for health education and communication without alarming the public.

During dengue epidemics, nursing and medical students together with community activists can visit homes with the double purpose of providing health education and actively tracing dengue cases. This has been shown to be feasible, inexpensive and effective (11) and must be coordinated with the primary health care units. It is useful to have printed information about dengue illness and the warning signs for distribution to members of the community. Medical care providers must include health education activities such as disease prevention in their daily work.

2.3.1. A stepwise approach to the management of dengue

(see Table 2.2)

2.3.1.2. Step II—Diagnosis, assessment of disease phase and severity

On the basis of evaluations of the history, physical examination and/or full blood count and haematocrit, clinicians should be able to determine whether the disease is dengue, which phase it is in (febrile, critical or recovery), whether there are warning signs, the hydration and haemodynamic status of the patient, and whether the patient requires admission (Textboxes E and F).

Textbox E

Admission criteria. enlarged, tender liver, although not yet in shock chest pain or respiratory distress, cyanosis

Textbox F

Discharge criteria (all of the following conditions must be present).

2.3.2. Treatment according to groups A–C

2.3.2.1. Group A – patients who may be sent home

(see the home care card for dengue in Textbox G)

Textbox G

Home care card for dengue. Adequate bed rest Adequate fluid intake (>5 glasses for average-sized adults or accordingly in children)

These are patients who are able to tolerate adequate volumes of oral fluids and pass urine at least once every six hours, and do not have any of the warning signs, particularly when fever subsides.

Ambulatory patients should be reviewed daily for disease progression (decreasing white blood cell count, defervescence and warning signs) until they are out of the critical period. Those with stable haematocrit can be sent home after being advised to return to the hospital immediately if they develop any of the warning signs and to adhere to the following action plan:

• Encourage oral intake of oral rehydration solution (ORS), fruit juice and other fluids containing electrolytes and sugar to replace losses from fever and vomiting. Adequate oral fluid intake may be able to reduce the number of hospitalizations (13). [Caution: fluids containing sugar/glucose may exacerbate hyperglycaemia of physiological stress from dengue and diabetes mellitus.]
• Give paracetamol for high fever if the patient is uncomfortable. The interval of paracetamol dosing should not be less than six hours. Tepid sponge if the patient still has high fever. Do not give acetylsalicylic acid (aspirin), ibuprofen or other non-steroidal anti-inflammatory agents (NSAIDs) as these drugs may aggravate gastritis or bleeding. Acetylsalicylic acid (aspirin) may be associated with Reye's Syndrome.
• Instruct the care-givers that the patient should be brought to hospital immediately if any of the following occur: no clinical improvement, deterioration around the time of defervescence, severe abdominal pain, persistent vomiting, cold and clammy extremities, lethargy or irritability/restlessness, bleeding (e.g. black stools or coffee-ground vomiting), not passing urine for more than 4–6 hours.

Patients who are sent home should be monitored daily by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, signs of plasma leakage and bleeding, haematocrit, and white blood cell and platelet counts (see group B).

2.3.2.2. Group B – patients who should be referred for in-hospital management

Patients may need to be admitted to a secondary health care centre for close observation, particularly as they approach the critical phase. These include patients with warning signs, those with co-existing conditions that may make dengue or its management more complicated (such as pregnancy, infancy, old age, obesity, diabetes mellitus, renal failure, chronic haemolytic diseases), and those with certain social circumstances (such as living alone, or living far from a health facility without reliable means of transport).

If the patient has dengue with warning signs, the action plan should be as follows:

• Obtain a reference haematocrit before fluid therapy. Give only isotonic solutions such as 0.9% saline, Ringer's lactate, or Hartmann's solution. Start with 5–7 ml/kg/hour for 1–2 hours, then reduce to 3–5 ml/kg/hr for 2–4 hours, and then reduce to 2–3 ml/kg/hr or less according to the clinical response (Textboxes H, J and K).
• Reassess the clinical status and repeat the haematocrit. If the haematocrit remains the same or rises only minimally, continue with the same rate (2–3 ml/kg/hr) for another 2–4 hours. If the vital signs are worsening and haematocrit is rising rapidly, increase the rate to 5–10 ml/kg/hour for 1–2 hours. Reassess the clinical status, repeat the haematocrit and review fluid infusion rates accordingly.
• Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Intravenous fluids are usually needed for only 24–48 hours. 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 that is/are adequate, or haematocrit decreasing below the baseline value in a stable patient.
• Patients with warning signs should be monitored by health care providers until the period of risk is over. A detailed fluid balance should be maintained. Parameters that should be monitored include vital signs and peripheral perfusion (1–4 hourly until the patient is out of the critical phase), urine output (4–6 hourly), haematocrit (before and after fluid replacement, then 6–12 hourly), blood glucose, and other organ functions (such as renal profile, liver profile, coagulation profile, as indicated).

Textbox H

Calculations for normal maintenance of intravenous fluid infusion.

Textbox J

Hourly maintenance fluid regime for overweight or obese patients.

Textbox K

Estimated ideal body weight for overweight or obese adults.

If the patient has dengue without warning signs, the action plan should be as follows:

• Encourage oral fluids. If not tolerated, start intravenous fluid therapy of 0.9% saline or Ringer's lactate with or without dextrose at maintenance rate (Textbox H). For obese and overweight patients, use the ideal body weight for calculation of fluid infusion (Textboxes J and K). Patients may be able to take oral fluids after a few hours of intravenous fluid therapy. Thus, it is necessary to revise the fluid infusion frequently. Give the minimum volume required to maintain good perfusion and urine output. Intravenous fluids are usually needed only for 24–48 hours.
• Patients should be monitored by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, haematocrit, and white blood cell and platelet counts (Textbox L). Other laboratory tests (such as liver and renal functions tests) can be done, depending on the clinical picture and the facilities of the hospital or health centre.

Textbox L

Example of a monitoring chart for dengue.

2.3.2.3. Group C – patients who require emergency treatment and urgent referral when they have severe dengue

Patients require emergency treatment and urgent referral when they are in the critical phase of disease, i.e. when they have:

–

severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress;

–

severe haemorrhages;

–

severe organ impairment (hepatic damage, renal impairment, cardiomyopathy, encephalopathy or encephalitis).

All patients with severe dengue should be admitted to a hospital with access to intensive care facilities and blood transfusion. Judicious intravenous fluid resuscitation is the essential and usually sole intervention required. The crystalloid solution should be isotonic and the volume just sufficient to maintain an effective circulation during the period of plasma leakage. Plasma losses should be replaced immediately and rapidly with isotonic crystalloid solution or, in the case of hypotensive shock, colloid solutions (Textbox M). If possible, obtain haematocrit levels before and after fluid resuscitation.

Textbox M

Choice of intravenous fluids for resuscitation. Based on the three randomized controlled trials comparing the different types of fluid resuscitation regime in dengue shock in children, there is no clear advantage to the use of colloids over crystalloids (more...)

There should be continued replacement of further plasma losses to maintain effective circulation for 24–48 hours. For overweight or obese patients, the ideal body weight should be used for calculating fluid infusion rates (textboxes J and K). A group and cross-match should be done for all shock patients. Blood transfusion should be given only in cases with suspected/severe bleeding.

Fluid resuscitation must be clearly separated from simple fluid administration. This is a strategy in which larger volumes of fluids (e.g. 10–20 ml boluses) are administered for a limited period of time under close monitoring to evaluate the patient's response and to avoid the development of pulmonary oedema. The degree of intravascular volume deficit in dengue shock varies. Input is typically much greater than output, and the input/output ratio is of no utility for judging fluid resuscitation needs during this period.

The goals of fluid resuscitation include improving central and peripheral circulation (decreasing tachycardia, improving blood pressure, pulse volume, warm and pink extremities, and capillary refill time <2 seconds) and improving end-organ perfusion – i.e. stable conscious level (more alert or less restless), urine output ≥ 0.5 ml/kg/hour, decreasing metabolic acidosis.

Treatment of shock

The action plan for treating patients with compensated shock is as follows (Textboxes D and N, Figure 2.2):

Figure 2.2

Algorithm for fluid management in compensated shock. HCT = haematocrit

• Start intravenous fluid resuscitation with isotonic crystalloid solutions at 5–10 ml/kg/hour over one hour. 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 for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, then to 2–3 ml/kg/hr, and then further depending on haemodynamic status, which can be maintained for up to 24–48 hours. (See textboxes H and J for a more appropriate 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 the haematocrit increases or is still high (>50%), repeat a second bolus of crystalloid solution at 10–20 ml/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 haematocrit decreases compared to the initial reference haematocrit (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible (see treatment for haemorrhagic complications).
• Further boluses of crystalloid or colloidal solutions may need to be given during the next 24–48 hours.

Patients with hypotensive shock should be managed more vigorously. The action plan for treating patients with hypotensive shock is as follows (Textboxes D and N, Figure 2.3):

Figure 2.3

Algorithm for fluid management in hypotensive shock.

• Initiate intravenous fluid resuscitation with crystalloid or colloid solution (if available) at 20 ml/kg as a bolus given over 15 minutes to bring the patient out of shock as quickly as possible.
• If the patient's condition improves, give a crystalloid/colloid infusion of 10 ml/kg/hr for one hour. Then continue with crystalloid infusion and gradually reduce to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, and then to 2–3 ml/kg/hr or less, which can be maintained for up to 24–48 hours (textbox H).
• If vital signs are still unstable (i.e. shock persists), review the haematocrit obtained before the first bolus. If the haematocrit was low (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible (see treatment for haemorrhagic complications).
• If the haematocrit was high compared to the baseline value (if not available, use population baseline), change intravenous fluids to colloid solutions at 10–20 ml/kg as a second bolus over 30 minutes to one hour. After the second bolus, reassess the patient. If the condition improves, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above. If the condition is still unstable, repeat the haematocrit after the second bolus.
• If the haematocrit decreases compared to the previous value (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible (see treatment for haemorrhagic complications). If the haematocrit increases compared to the previous value or remains very high (>50%), continue colloid solutions at 10–20 ml/kg as a third bolus over one hour. After this dose, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above when the patient's condition improves.
• Further boluses of fluids may need to be given during the next 24 hours. The rate and volume of each bolus infusion should be titrated to the clinical response. Patients with severe dengue should be admitted to the high-dependency or intensive care area.

Patients with dengue shock should be frequently monitored until the danger period is over. A detailed fluid balance of all input and output should be maintained.

Parameters that should be monitored include vital signs and peripheral perfusion (every 15–30 minutes until the patient is out of shock, then 1–2 hourly). In general, the higher the fluid infusion rate, the more frequently the patient should be monitored and reviewed in order to avoid fluid overload while ensuring adequate volume replacement.

If resources are available, a patient with severe dengue should have an arterial line placed as soon as practical. The reason for this is that in shock states, estimation of blood pressure using a cuff is commonly inaccurate. The use of an indwelling arterial catheter allows for continuous and reproducible blood pressure measurements and frequent blood sampling on which decisions regarding therapy can be based. Monitoring of ECG and pulse oximetry should be available in the intensive care unit.

Urine output should be checked regularly (hourly till the patient is out of shock, then 1–2 hourly). A continuous bladder catheter enables close monitoring of urine output. An acceptable urine output would be about 0.5 ml/kg/hour. Haematocrit should be monitored (before and after fluid boluses until stable, then 4–6 hourly). In addition, there should be monitoring of arterial or venous blood gases, lactate, total carbon dioxide/bicarbonate (every 30 minutes to one hour until stable, then as indicated), blood glucose (before fluid resuscitation and repeat as indicated), and other organ functions (such as renal profile, liver profile, coagulation profile, before resuscitation and as indicated).

Changes in the haematocrit are a useful guide to treatment. However, changes must be interpreted in parallel with the haemodynamic status, the clinical response to fluid therapy and the acid-base balance. For instance, a rising or persistently high haematocrit together with unstable vital signs (particularly narrowing of the pulse pressure) indicates active plasma leakage and the need for a further bolus of fluid replacement. However, a rising or persistently high haematocrit together with stable haemodynamic status and adequate urine output does not require extra intravenous fluid. In the latter case, continue to monitor closely and it is likely that the haematocrit will start to fall within the next 24 hours as the plasma leakage stops.

A decrease in haematocrit together with unstable vital signs (particularly narrowing of the pulse pressure, tachycardia, metabolic acidosis, poor urine output) indicates major haemorrhage and the need for urgent blood transfusion. Yet a decrease in haematocrit together with stable haemodynamic status and adequate urine output indicates haemodilution and/or reabsorption of extravasated fluids, so in this case intravenous fluids must be discontinued immediately to avoid pulmonary oedema.

Treatment of haemorrhagic complications

Mucosal bleeding may occur in any patient with dengue but, if the patient remains stable with fluid resuscitation/replacement, it should be considered as minor. The bleeding usually improves rapidly during the recovery phase. In patients with profound thrombocytopaenia, ensure strict bed rest and protect from trauma to reduce the risk of bleeding. Do not give intramuscular injections to avoid haematoma. It should be noted that prophylactic platelet transfusions for severe thrombocytopaenia in otherwise haemodynamically stable patients have not been shown to be effective and are not necessary (14).

If major bleeding occurs it is usually from the gastrointestinal tract, and/or vagina in adult females. Internal bleeding may not become apparent for many hours until the first black stool is passed.

Patients at risk of major bleeding are those who:

–

have prolonged/refractory shock;

–

have hypotensive shock and renal or liver failure and/or severe and persistent metabolic acidosis;

–

are given non-steroidal anti-inflammatory agents;

–

have pre-existing peptic ulcer disease;

–

are on anticoagulant therapy;

–

have any form of trauma, including intramuscular injection.

Patients with haemolytic conditions are at risk of acute haemolysis with haemoglobinuria and will require blood transfusion.

Severe bleeding can be recognized by:

–

persistent and/or severe overt bleeding in the presence of unstable 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 blood pressure, especially in those with severe abdominal tenderness and distension.

Blood transfusion is life-saving and should be given as soon as severe bleeding is suspected or recognized. However, blood transfusion must be given with care because of the risk of fluid overload. Do not wait for the haematocrit to drop too low before deciding on blood transfusion. Note that haematocrit of <30% as a trigger for blood transfusion, as recommended in the Surviving Sepsis Campaign Guideline (15), is not applicable to severe dengue. The reason for this is that, in dengue, bleeding usually occurs after a period of prolonged shock that is preceded by plasma leakage. During the plasma leakage the haematocrit increases to relatively high values before the onset of severe bleeding. When bleeding occurs, haematocrit will then drop from this high level. As a result, haematocrit levels may not be as low as in the absence of plasma leakage.

The action plan for the treatment of haemorrhagic complications is as follows:

• Give 5–10ml/kg of fresh-packed red cells or 10–20 ml/kg of fresh whole blood at an appropriate rate and observe the clinical response. It is important that fresh whole blood or fresh red cells are given. Oxygen delivery at tissue level is optimal with high levels of 2,3 di-phosphoglycerate (2,3 DPG). Stored blood loses 2,3 DPG, low levels of which impede the oxygen-releasing capacity of haemoglobin, resulting in functional tissue hypoxia. A good clinical response includes improving haemodynamic status and acid-base balance.
• Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in haematocrit after blood transfusion. There is little evidence to support the practice of transfusing platelet concentrates and/or fresh-frozen plasma for severe bleeding. It is being practised when massive bleeding can not be managed with just fresh whole blood/fresh-packed cells, but it may exacerbate the fluid overload.
• Great care should be taken when inserting a naso-gastric tube which may cause severe haemorrhage and may block the airway. A lubricated oro-gastric tube may minimize the trauma during insertion. Insertion of central venous catheters should be done with ultra-sound guidance or by a very experienced person.

2.3.3. Treatment of complications and other areas of treatment

2.3.3.3. Supportive care and adjuvant therapy

Supportive care and adjuvant therapy may be necessary in severe dengue. This may include:

–

renal replacement therapy, with a preference to continuous veno-venous haemodialysis (CWH), since peritoneal dialysis has a risk of bleeding;

–

vasopressor and inotropic therapies as temporary measures to prevent life-threatening hypotension in dengue shock and during induction for intubation, while correction of intravascular volume is being vigorously carried out;

–

further treatment of organ impairment, such as severe hepatic involvement or encephalopathy or encephalitis;

–

further treatment of cardiac abnormalities, such as conduction abnormalities, may occur (the latter usually not requiring interventions).

In this context there is little or no evidence in favour of the use of steroids and intravenous immunoglobulins, or of recombinant Activated Factor VII.

Refer to standard textbooks of clinical care for more detailed information regarding the treatment of complications and other areas of treatment.

DENGUE CASE MANAGEMENT (PDF, 457K)