Dengue is an arboviral infection that affects humanscausing significant morbidity and mortality in tropical countries. Our first patient who had diabetes presented with shock and was managed as dengue hemorrhagic fever with superadded sepsis which required noradrenalin plus broad-spectrum intravenous antibiotics. The second patient developed severe bradycardia during the ascending limb of the critical phase with hemodynamic stability, which recovered on discharge. Third patient presented with severe and rapid leaking; we used intravenous albumin as an alternative colloid with good outcome. The fourth patient was a pregnant mother at term, and she went into spontaneous labor during the latter half of the critical phase. The fifth patient developed dengue hemorrhagic fever complicated with probable haemophagocytic lymphohistiocytosis. She was treated with intravenous steroids andimmunoglobulin, yet succumbed on day 7.
Dengue fever is the most prevalent arboviral infection that affects humans with significant mortality. It has four serotypes that demonstrate various clinicopathologic manifestations in the human body, leading to different presentations and complications with unpleasant sequelae. Management of dengue fever in Sri Lanka is done according to the national guidelines published by the Ministry of Health in 2012 that was updated in 2018. However, atypical presentations and unusual complications fall beyond the scope of current guidelines that can push the clinician into unfamiliar terrain. This case series describes five unusual complications of dengue fever and different management strategies adopted at a single center in Sri Lanka. All five patients in this case series had serologically confirmed dengue fever and presented to Sri Jayewardenepura General Hospital (SJGH) in the latter half of 2019. They were all females aged between 23 and 65 years.
A 53-year-old diabetic patient presented with fever for five days. She had arthralgia and myalgia with no focal symptoms in keeping with a viral infection. Examination revealed right hypochondrial tenderness and clinical evidence of leaking. Her peripheries were warm, and she was haemodynamicaly stable. On admission, her hematologic indices showed leucopenia and thrombocytopenia (white blood cell count (WBC) of 3300/
She was considered to be in the ascending limb of the critical phase and managed with intravenous normal saline 50 ml and oral fluid 50 ml per hour with dengue critical-phase monitoring. Her blood sugar on admission was 183 mg/dl. It was controlled with regular subcutaneous soluble insulin injections.
Six hours later, her blood pressure dropped to 77/55 mm/Hg without tachycardia. Surprisingly, her pulse was bounding and CRFT (capillary refill time) was <2 seconds. She had no fever or chest pain. Her urine output maintained adequately probably owing to hyperglycemia.
Initial fluid resuscitation was carried out with two crystalloid boluses of normal saline at 5 ml/kg given rapidly followed by intravenous dextran 5 ml/kg over 30 minutes. Since the PCV drop was steep, we transfused blood (5 ml/kg/hour). Her ECG was normal without conduction blocks. Troponin I was normal. Her serum electrolytes including ionized calcium was within normal limits (Ca2+: 1.1 mmol/). The C-reactive protein (CRP) level was elevated at 40 ng/ml. 2D echo showed EF 60% without evidence of myocarditis. Following fluid resuscitation, she had persistent low blood pressure with good pulse pressure without tachycardia.
We suspected superadded sepsis with dengue hemorrhagic fever and started her on inotropic support with intravenous noradrenaline. Due to her underlying plasma leakage, we restricted initial fluid resuscitation to the minimal volume to prevent fluid overload. We started intravenous meropenem 1 g 8 hourly after taking blood and urine for culture. Rest of the critical phase was managed with intravenous crystalloid and oral fluids accordingly. She recovered completely on day 7 and discharged on day 8.
A 34-year-old previously healthy woman presented on the second day of fever. Her NS1 antigen test was positive. She was managed as dengue hemorrhagic fever because she had sonographic evidence of leakage. During the ascending limb of the critical period, she developed sinus bradycardia with the lowest heart rate of 37 beats per min (bpm). She remained haemodynamically stable.
Her troponin I was negative. 2D echocardiogram was normal, and ejection fraction was >60%. Her thyroid functions were TSH: 3.084 mIU/L and T4: 1.21 mIU/L.
We started her on oral orciprenaline 5 mg bd after discussing with the consultant electrophysiologist. Later, the dose was doubled to maintain her heart rate above 60bpm. Once she recovered from dengue hemorrhagic fever, her heart rate picked up and orciprenalin dose was gradually tailed off over 48 hours. The critical period was otherwise uneventful. Subsequent 24-hour holter monitoring done two weeks after recovery was normal.
We concluded this to be a case ofdengue fever-associated sinus node dysfunction.
A 23-year-old previously healthy woman presented with typical symptoms of dengue fever on day 2 with positive NS1 antigen test. On admission, her WBC was 2900/
During the middle of the dengue critical phase (20 hours), she developed tachycardia (heart rate was 127 beats/min) with a narrow pulse pressure of 27 mmHg. Her urine output was reduced to <0.5 ml/kg/hour for 3 hours. Her hematocrit had risen up to 57% (baseline 45%). She had clinical features of fluid overload with bilateral moderate pleural effusions. At this point, we had already given the total dextran quota for 24 hours (3 × 10 ml/kg). We had given total fluid quota of 3550 ml.
Her serum albumin level was 1.7 g/dL. We took expert opinion and gave intravenous salt poor albumin 100 ml over one hour. Her parameters including tachycardia, narrow pulse pressure, and urine output improved after the albumin bolus.
We repeated albumin boluses of 100 ml at 25th and 39th hour of the critical phase. We reduced oral intake 25 ml to 50 ml per hour in between albumin boluses to prevent further fluid overload. We did not use any intravascular crystalloids during this period. The patient recovered and was discharged safely on day 8.
A 34 year-old woman during her second pregnancy presented at 37 weeks of POA with fever on day 3 and positive NS1 antigen test. She developed progressive thrombocytopenia below 100,000/
A multidisciplinary discussion was done involving the hematology, transfusion medicine, and obstetric teams. Final decision was to proceed with immediate lower segment caesarian section.
A manual platelet count was done just before surgery. It was 54,000/
A 27-year-old woman presented with NS1 antigen positive dengue fever on day 3. She had ultrasound evidence of leaking on admission and was managed as dengue hemorrhagic fever. Unusually, her fever spikes persisted along with bicytopenia (platelet 15000/
She had significant elevated hepatic transaminases (AST 12841 U/L and ALT 3034 U/L). Screening for acute viral hepatitis was negative. Serum ferritin was 136,459 ng/mL. Her blood picture showed dengue hemorrhagic fever with superadded bacterial infection. USS abdomen detected free fluid in pelvis without hepatomegaly or splenomegaly. Her cardiac function was good with normal 2D echo and an ejection fraction of 60%. ROTEM (rotational thromboelastography) showed severe coagulation derangement. Her CRP was 13 and blood cultures remained negative.We transfused her fresh frozen plasma, platelet, and cryoprecipitate and started her on intravenous Ceftriaxone. Clinical diagnosis of hemophagocytic lymphohistiocytosis was considered. Bone marrow aspiration was not done because the patient had high risk of bleeding and she was haemodynamically unstable. We treated her with IV methylprednisolone 1 g daily and IV immunoglobulin (0.4 g/kg/daily)for one day. However, she developed multiorgan failure with acute kidney injury. She succumbed on day 7.
Dengue is a dynamic disease with variable presentations and an array of direct and indirect complications. Management of dengue fever in Sri Lanka is based on national dengue guidelines. It relies on prompt identification of plasma leakage or the onset of the critical phase, meticulous monitoring of parameters, fluid management and accurate recognition of the convalescent phase/fluid reabsorption. However, the sheer diversity of the clinico-pathologic outcomes of dengue fever underscores the importance of clinical experience to manage these clinical roadblocks. The above five case scenarios describe unusual complications of dengue fever and different management strategies applied for the complications.
Dengue hemorrhagic fever has three main phases. Febrile phase, critical phase, and recovery phase [
During the recovery phase, patients’ general wellbeing is improved and leaked fluid will be reabsorbed to the intravascular system [
The first case is of dengue hemorrhagic fever and persistent shock not responding to guideline-based fluid resuscitation. The presence of bounding pulse and preserved pulse pressure with a low diastolic blood pressure is not in keeping with plasma leakage seen in dengue fever [
Low blood pressure due to sepsis requires a large volume fluid resuscitation (30 ml/kg in first hour) with crystalloid boluses [
Dengue-related cardiac dysfunctions are quite uncommon [
Rapid and prolonged plasma leakage is a stressful situation to the clinician. It is impossible to limit to the allocated fluid quota if the patient is hemodynamically unstable. On the other hand, overtreatment with crystalloids leads to fluid overload which undermines perfusion. When the patient enters the descending limb of the critical phase, fluid which leaked before will spontaneously reabsorb to the circulation. Our third patient’s leaking phase was quite prolonged. She had persistent tachycardia, rising hematocrit, and low urine output in keeping with severe plasma leakage. Plasma leakage is known to have low albumin [
Dengue in pregnancy is challenging because of the altered physiology compared to a healthy nonpregnant woman. Our patient went into spontaneous labor during the descending limb of the dengue critical phase. Mode of delivery during the critical phase of dengue is decided in favor of the mother’s life irrespective of the outcome of the baby [
Haemophagocytic lymphohistiocytosis (HLH) describes a clinical syndrome of hyperstimulation and ineffective immune response to infection or malignancy [
Dengue is an extremely challenging and dynamic disease, which can lead to many unusual complications. Some of these complications can be fatal and require high index of suspicion to diagnose and treat promptly.
The authors declare no conflicts of interest.