4.6 Special Clinical Situations

• Impact on physiology of pregnancy.
• Cardiovascular - tachycardia, lower blood pressure.
• Hematological - lower HcT at 3rd trimester.
• HCO3 (Bicarbonate) level - lower.

The following physiological changes in pregnancy may make the diagnosis and assessment of plasma leakage challenging:

• Elevation of HcT in dengue is marked by hemodilution due to increase in plasma volume especially in the 2nd and 3rd trimester.
• Serial HcT measurement is crucial for disease monitoring in pregnancy.
• The detection of third space fluid accumulation is difficult due to the presence of gravid uterus.
• Baseline blood pressure is often lower and pulse pressure wider.
• Baseline heart rate may be higher.

Impact of dengue on pregnancy and delivery.

• Early Abortion (3%-13%).
• Embryopathy specially neural tube defect.
• Antepartum haemorrhage (APH) due to retro placental hemorrhage or abruptio placenta.
• Preterm birth (3%-33%).
• Low-birth weight (9%-16%).
• IUGR. 
• Fetal Distress.
• IUD or Still birth (4.7%-13%.).
• Increased incidence of caesarean deliveries.
• Post-Partum Haemorrhage (PPH).

New born presentation

• Fever
• Hepatomegaly
• Thrombocytopenia
• Circulatory insufficiency

Causes of Maternal death

• Sever Antepartum Hemorrhage (APH)
• Sever Post-partum Hemorrhage (PPH)
• Dengue shock syndrome (DSS)
• Multi organ failure (MOF)

Causes of Fetal death

• Fetal distress
• Fetal circulatory insufficiency
• Fetal coagulopathy

Fetal well-being evaluation

USG of pregnancy profile

• Gestational age
• Fetal Heart Rate (FHR)
• Fetal weight
• Fetal Presentation
• AFI
• Placental position and maturation

Biophysical profile

BPP Scoring interpretation and management

Note - When the patient in critical phase then we will try to delay the delivery to prevent complications.

Admission is required and close follow up with CBC daily is very important

The gestation and the phase of dengue are important factors in determining the management. A multi-disciplinary team consisting of obstetricians, physician, anesthetist and the paediatrician should get involved in the management.

• When a Suspected dengue (febrile patient) is first seen, look for warning signs and admit if anyone is found.
• If admitted to the obstetric ward urgent referral to the physician is essential.
• Explanation to the family members about the course of DHF and the management is important.

The signs, symptoms and lab investigations may be confused with other complications of pregnancy such as toxaemia and HELLP syndrome (Haemolysis, Elevated Liver Enzymes and Low Platelets). It is essential to consider the possibility of dengue in a patient with features of HELLP. Increased incidence of abruptio placentae, death in-utero and prematurity are reported.

Complication:

• Premature fetal loss or vertical transmission in Dengue infection may be one of the grave fetal complications in pregnancy.
• The vertical transmission in fetus is evidenced by fever, thrombocytopenia, raised liver enzymes, gastric bleeding, pleural effusion, convalescent rash and Dengue specific IgM (+).
• The important maternal complications include thrombocytopenia, raised liver enzymes, febrile illness, gum bleeding and bilateral pleural effusions.
• Moreover, uncomplicated pregnancy may be complicated with DHF.
• Delivery should be conducted in a tertiary hospital where all advanced facilities are available.

The normal physiological changes in pregnancy make the diagnosis and assessment of plasma leakage difficult. Therefore, the following baseline parameters should be noted as early as possible on the first day of illness:

• Pulse, blood pressure (BP), pulse pressure. (Baseline BP is often lower and pulse pressure wider & heart rate may be higher)
• CBC - (Haemoglobin, HCT & platelet count may be lower than in nonpregnant patient)
• SGOT/SGPT
• Clinical detection of pleural effusion and ascites may be difficult due to the presence of gravid uterus. Use of Ultra Sound Scan to detect the following, is advisable
• Pleural effusion
• Ascites (Gallbladder wall oedema may be seen in both DF & DHF)

Generally, the presentation and clinical course of dengue in pregnant women is similar to that in non-pregnant individuals. The fluid volume for the critical period (M+5%) for a pregnant mother should be calculated (based on the weight prior to pregnancy)

Management of pregnant patients with DF/DHF close to delivery

Risk of bleeding is at its highest during the period of plasma leakage (critical phase). Therefore, unless to save mothers life, avoid Lower uterine segment Caesarean Section (LUCS) or induction of labour during the Critical (plasma leakage) phase. Obstetric procedures (such as amniocentesis or external cephalic version) should be avoided during the illness. If obstetric procedures are to be undertaken,

• Maintain the platelet count above 50,000/mm³ Single donor platelet transfusion is preferred, if available.
• If patient goes into spontaneous labour during critical phase take steps to prevent vaginal tears by performing an episiotomy.
• In a case of fetal compromise priority should be given to the mother’s life and decision making should involve the multidisciplinary team.
• Counseling the family on the probable outcome is essential.

Management of patients with DF/DHF during immediate postpartum

Dengue fever should be suspected in patients having fever in the immediate post-partum period since this may be overlooked. Early referral to a physician is recommended.

Clinical manifestations

• Little is known about dengue in the elderly.
• Clinical manifestations of dengue in the elderly are similar to those of younger adults.
• However, rash, hepatomegaly and mucocutaneous hemorrhage are less frequent but gastrointestinal tract bleeding and microhaematuria are more common.
• The elderly has significantly lower incidences of fever, abdominal pain, bone pain and rashes.
• Higher frequencies of concurrent bacteraemia, gastrointestinal bleeding, acute renal failure, and pleural effusion.
• Higher incidence of prolonged prothrombin time and lower mean haemoglobin levels than younger adult patients.
• A higher incidence of plasma leakage and case fatalities has been reported in the elderly compared to young adult dengue patients

Issues in management

• About 10% of elderly dengue patients may have no complaints of fever
• Higher rate of acute renal failure
• The impact of increased co-morbidities.
• Ageing-related decline in cardiopulmonary function is another important consideration during fluid replacement and/or resuscitation in dengue illness.
• Complications such as congestive heart failure and acute pulmonary oedema may occur.
• Frequent assessments and adjustments of the fluid regime are required to avoid or to minimize such complications.

Symptoms:

fever, runny nose, cough, loose motion, vomiting, seizures, Signs: high fever, sore throat, dehydration, bulged fontanel, neck rigidity, hepatomegaly, splenomegaly.

Investigations:

Leukopenia unlikely, positive NS1 during febrile period, IgM positive during defervescence, hypoglycemia, hyponatremia, hypocalcemia, raised AST.

USG: hepato-splenomegaly, ascites

CXR: pleural effusion

Treatment

• Home care
• Caution on over hydration
• Insecticide-treated mosquito net for the infants who sleep by day Hospital care Fluid restriction (infants have shorter duration of plasma leakage)
• Frequently evaluated for oral fluid intake and urinary output (catheterization needed)
• Fluid therapy during the plasma leakage phase
• Half strength normal saline in 5% dextrose for < 6 months infants; normal saline in 5% dextrose in infants > 6 months
• Colloids (dextran 40) should be considered when high rates of crystalloids are required

• If surgery is mandatory in a patient with DHF, proper assessment of the patient, hematological and biochemical investigations should be available immediately prior to surgery.
• Fresh blood and or platelet concentrate also has to be made available prior to surgery.
• Platelet count should be raised up to 100000/mm³.
• Fluid replacement should be according to stage the of DHF. Other treatment is to be given as usual tailored to the need.

• The disease may be decompensated in DHF who was well compensated before Dengue episode.
• As DHF involves in hepatic enzyme elevation so critical patient care and regular LFT should be done.
• Decompensated CLD should be managed as non-infected patient.
• Platelet concentrate & fresh blood maybe required. Patient should be treated in a hospital where facilities are available.

• Dengue patients with Chronic Kidney Disease (CKD) have a significantly higher risk of severe dengue and mortality. The outcome correlates with the renal function.
• The warning signs of severe dengue are similar to those of uraemia in CKD.
• Ascites and/or pleural effusion, and signs of plasma leakage in dengue, are not uncommon findings in patients with CKD and fluid retention.
• The ambiguity of these symptoms and signs could delay the recognition of plasma leakage and severe dengue.
• Patients with CKD have a low baseline haematocrit and platelet count
• A low baseline platelet count is not an uncommon finding in dialysis patients.

Challenges in fluid management:

• Narrow window of fluid tolerance: Patients with CKD have limited fluid tolerance. Frequent assessments of the haemodynamic state and frequent fluid regime adjustments are mandatory.
• Urine output: The urine output should not be used as an indicator of the intravascular volume status because patients with CKD can have either low or high urine-output renal failure. Low urine output in CKD contributes to the risk of fluid overload whereas high urine output may aggravate hypovolaemia.
• Limited effect of diuretics: Diuretics have a limited effect in CKD, making patients more susceptible to fluid overload. Dialysis may be required.
• Patient on MHD preferably dialysis session should be deferred.

Acid base balance and electrolyte balance

Patients with CKD are at risk of metabolic acidosis and electrolyte imbalance which will become worse during dengue shock. If these persist after adequate fluid replacement, dialysis may be considered after haemodynamic stability is achieved.

Platelet dysfunction

Platelet dysfunction, well recognized in CKD together with severe thrombocytopenia with or without coagulopathy, predispose the dengue patient to severe bleeding that may be difficult to control.

• Congenital or acquired cardiac lesions such as valvular heart disease or ischaemic heart disease, especially the later, are common co-morbidities in adults or the elderly.
• In dengue with high fever, tachycardia and increased metabolic demands may precipitate decompensation of cardiac functions.
• Such patients have limited ability to compensate for hypovolaemia or hypervolaemia.
• Fluid therapy should be guided by frequent clinical assessments, haematocrit and blood gas determinations.
• Patients with cyanotic heart diseases have polycythemia and a high baseline haematocrit.
• Non-invasive positive pressure ventilation should be considered to support patients with cardiac decomposition. Failing this, mechanical ventilation should be instituted.
• Loop diuretics should be used cautiously and in a timely way: after achieving haemodynamic stability when intravenous fluid therapy has been discontinued or reduced and in patients with fluid overload.

Ischemic Heart Disease

• Aspirin/clopidogrel should be avoided for certain days, until the patient recovers from DHF.
• Patients with IHD are more prone to cardiac dysrhythmia, cardiac failure and thrombo-embolism.

Interpretation of BP:

• Hypotension is a late sign of shock. However, in patients with uncontrolled hypertension a BP reading that is considered normal for age may, in reality, be low for patients with uncontrolled hypertension.
• What is considered as “mild” hypotension may in fact be profound.
• Patients with chronic hypertension should be considered to be hypotensive when the mean arterial pressure (MAP) declines by 40 mmHg from the baseline, even if it still exceeds 60 mmHg. (For example, if the baseline MAP is 110 mmHg, a MAP reading of 65 mmHg should be considered as significant hypotension).
• Look for other manifestations of shock.

Management Issue:

• ß-blockers, a common antihypertensive medication, cause bradycardia and may block the tachycardic response in shock. The heart rate should not be used as an assessment of perfusion in patients on ß-blockers.
• Antihypertensive agents such as calcium channel blockers may cause tachycardia. Tachycardia in these patients may not indicate hypovolemia.
• Knowing the baseline heart rate before the dengue illness is helpful in the haemodynamic assessment.

The Impact on Hypotension:

• The continuation of antihypertensive agents during the acute dengue illness should be evaluated carefully during the plasma leaking phase.
• The BP lowering effects of these agents and diuretic therapy may exacerbate the hypotension and hypoperfusion of intravascular volume depletion.

• Hyperglycaemia results in osmotic diuresis and worsens intravascular hypovolaemia.
• Not correcting the hyperglycaemic state exacerbates the shock state
• Hyperglycaemia also puts patients at risk of bacterial infection.

Diabetic ketoacidosis and hyperosmolar hyperglycaemia:

• Clinical manifestations of diabetic ketoacidosis and hyperosmolar hyperglycaemia (nausea, vomiting and abdominal pain) are similar to the warning signs of severe dengue.
• It is not uncommon for dengue shock to be misdiagnosed as diabetic ketoacidosis.

Hypoglycaemia:

• Hypoglycaemia may occur in those patients taking oral hypoglycaemic gents (e.g. long-acting sulphonylurea), but who had poor oral intake.
• Hypoglycaemia could be aggravated by severe hepatitis from dengue.
• Oral hypoglycaemic agents: Gastrointestinal absorption of oral hypoglycaemic agents is unreliable because of vomiting and diarrhoea during the dengue illness.
• Some hypoglycaemic agents such as metformin may aggravate lactic acidosis, particularly in dengue shock. These agents should be avoided or discontinued during dengue shock and also in those with severe hepatitis.

Management

• Dengue patients with known diabetes mellitus should be admitted for closer monitoring of the diabetic as well as dengue states.
• If the patient has gastrointestinal disturbances, blood glucose should be controlled with intravenous short-acting insulin during the dengue illness.
• A validated protocol for insulin dose adjustments to a target glucose level of < 150 mg/dl (8.3 mmol/L) should be used.
• A source of glucose may be maintained once the target is achieved while receiving intravenous insulin.
• Blood glucose should be monitored every 1–2hours until glucose values and insulin rates are stable and then every 4 hours thereafter.

In this situation steroid should not be abruptly stopped. But if necessary, equivalent dosage may be given per IV route during the DS period.

High flow rate of fluid of room temperature may cause shivering, that needs fluid to be warmed up to near body temperature to avoid that which may create discomfort and terrorize the patient or attendant and jeopardize the management as well. In some instances, hypersensitivity or anaphylaxis may occur for which immediate standardntreatment of hypersensitivity and anaphylaxis should be instituted.

In any global clinical crisis (i.e. pandemic, epidemic) some diseases can represent symptoms like DF. ‘Dengue’ has been pandemic in many countries around the world. Dengue widely affected in countryside areas, urban poor regions, and suburbs areas.

During such situation patient’s history is more important. Signs & symptoms and laboratory investigations should be done accordingly. Physicians should take necessary steps according to his/her clinical suspicion.

As example; Dengue fever and COVID-19 are difficult to distinguish because they share some same clinical and laboratory features. Some authors described cases who were wrongly diagnosed as dengue but later confirmed to be COVID-19. Besides, co-infections with arboviruses and SARS-CoV-2 have not been well studied. There may scarcity of intensive care units to accommodate hospitalized patients with COVID-19, specific diagnostic tests, especially the RT-PCR, would also make it challenging to perform early detection of virus importation and prevent onward transmission. Another concern lies in the costs of hospitalization due to dengue fever. COVID-19 alone has a great potential to overwhelm the health system. If it is accompanied by dengue fever, this burden would have been even greater.

In these special situations or other upcoming similar unforeseen conditions not experienced before the following general rule may be adopted:

• Assessment and management by risk versus gain approach
• Frequent consultations with peers of relevant specialties
• If necessary multidisciplinary team management
• Patient should be hospitalized under close monitoring
• Searching for references and evidence of similar conditions
• Keep document and arrange for dissemination, publication or communication

Some PEARLs may help for taking some spot decision, these are:

• Leukocyte count has a very important prognostic guide in early phase of d e n g u e infection. Leucopenia < 5000 cells/mm³ indicates that within the next 24 hours the patient will have no fever and he will be entering the critical phase.
• What should not be done is as important as what should be done and what should be done should not be overdone.
• Hemorrhage during febrile phase signifies DF with unusual hemorrhage and possibly not DHF. But hemorrhage without fever should be critically assessed for DHF.
• Multiplying Hb level by 3 is usually found to be around the HcT level.
• Sudden pallor signifies internal bleeding.
• When HcT cannot be done or is not available the following clinical tips may help to speculate in DHF setting:
  • If the patient has/ had deep/massive bleeding from gut or other sites the possibility is that the patient may have lower HcT because of blood loss.
  • If the patient has/had surface/mild bleeding the possibility is that the patient may have higher HcT.
  • Sudden unexplained deterioration of hemodynamic status and or refractory to adequate fluid therapy the possibility is more of blood loss and hence low HcT level.
• In any complicated situation frequent consultations with other colleagues and multi-disciplinary team approach are useful.