Mortality review on Fulminant Varicella Infection
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Mortality review on Fulminant Varicella Infection



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  • Walk-in to Emergency department, seen in Yellow Zone
  • It is possible that smokers have an enhanced primary viraemia, secondary to the effects of smoking on the nasal mucosa, and this predisposes pneumonia. Furthermore, a previous report has shown that smoking renders human alveolar macrophages more susceptible to infection by herpes viruses, which could be relevant pathogenetically, although this requires further study.
  • Varicella-Zoster Virus Infection Associated with Acute Liver Failure,
  • The mechanisms involved in this fulminant visceral dissemination in the patients described remains unclear but are most likely related more to the impaired immune function than to the virulence of the VZV strain.
  • Some case report review suggest steroid pulse therapy in severe conditoin ( IV methyprednisolone 1000mg/day x 3 days)
  • I wish you that this CNY 2013 bring u the warmth of love, and the light of wisdomIn your life , unlimited Happiness of life

Mortality review on Fulminant Varicella Infection Mortality review on Fulminant Varicella Infection Presentation Transcript

  • Mortality Review (January 2013) Dr Nor Hidayah Zainool AbidinINTERNATIONAL ISLAMIC UNIVERSITY OF MALAYSIA HOSPITAL SULTAN ABDUL HALIM copyright to anor hidayah
  • 14/2/2013 @ 10:06• 29 year old gentleman Diagnosed with DM (2 years ago) - only have history of taking traditional medications in liquid form, not on proper follow-up• Not taking any new medications, traditional or otherwise recently• He started having rash on head 3 days ago along with fever and upper abdominal pain Rash then spread to face, trunk and bilateral upper limbs and going downwards Now involved bilateral lower limbs• Also having mild URTI symptoms - cough No diarrhea , No vomiting• No alterations in bladder habits and bowel habits• No past surgical history, No allergy• Single Doing his own business - nursery Non smoker and non alcoholic copyright to anor hidayah
  • Examination in Yellow Zone• alert ,pink not tachypnoiec hydration good lungs: clear abdomen: soft , non tender• Noted vesicular rash over the skull , abdomen , upper limbs• BP:134/78 SpO2: 100% under room air P:86 Temp:37.4• DXT :16.2• ECG: normal SR copyright to anor hidayah
  • • Initially treated as GERD• IV ranitidine 50mg STAT Syrup MMT 30 ml STAT IV drip 1 pint NS Observe in ED Observation bay WBC 9.5 Na+ 127 CK 215 HB 17.2 K+ 3.5 AST 604 PCV 50.2% Crea 77 LDH 1026 plt 175 urea 4.2 neu 77.6% Cl- 98 copyright to anor hidayah
  • 30 mins later in Yellow zone• still having upper abdominal pain more on right hypochondriac pain• alert ,pink not tachypnoiec bp:147/71 pr:64 temp:37.6 dxt:12.6• TAS done in ED : Gallbladder stone ? Treat as Cholitihiasis copyright to anor hidayah
  • clerked 2 hours after admission to surgical ward• Alert , concious not tachypneic , dehydrated BP : 142/ 91 P : 78 T : 37 Sp02 : 100 % under RA• Noted vesicopapular rash over the facial region, thorax and abdomen and back• Lungs clear, CVS DRNM• Tender over the epigastric region• Started on IVD 3 pint NS /day copyright to anor hidayah
  • Seen by surgical MO 3 hours later• Normal vital signs• Tender epigastric• NR for hepatitis B, hepatitis C virus and RVD pro 78• planned for US urgent cm thus KNBM alb 42 IV pantoprazole 40mg BD glo 36 ALT 776 ALP 66 treated with IM pethidine 75mg PRN Tot Bil 19• then given IM pethidine 100mg stat – in the morning as pt still having abdominal pain copyright to anor hidayah
  • 15/1/2013 @ 7:27 am• alert , concious not tachypneic BP: 125/76 PR:71 T : 37.4 Sp02 : 98 % under RA DXT : 10.3 abdomen : soft , pain over deep palpation over the epigastric region• started on T metformin 500mg by HO• was off on 17/1/2013• US abdomen was performed on 15/1/2013: LIVER: Slightly enlarged with increased in echogenicity and slight coarse echotexture of parenchyma.• Borderline hepatomegaly with fatty liver copyright to anor hidayah
  • copyright to anor hidayah
  • seen by medical MO @ 6:30pm• o/e alert, concious, not tachypnoeic BP:152/88 HR:81 SPO2: 100 Amylase 71 T:38 Diastase 373• Lungs: clear CVS: DRNM Abdomen soft, non-tender, liver palpable 2 FB + maculopapular rash on face trunk and back blanches, no discharges• Treated with IVD 4 pints normal saline over 24 hours Cover with IV Rocephine 2 g stat and 1 g BD• s/b medical specialist:: cont management• Still on IM pethidine 50 mg QID, At 11pm - Cap Tramal 50mg stat copyright to anor hidayah
  • Seen by surgeon 16/1/2013 @ 9:15• Having pain over the back Na+ 127  123 CK 215  1353 No vomiting mild abdominal pain K+ 3.5  4.5 AST 604  4565 alert Creat 77 85 LDH 1026 conscious 3325 BP:151/85 urea 4.2  5.6 P:88 T:38 Cl- 98 95 SpO2:99 Abdomen: pro 78  72 soft, tender on deep palpation alb 42 39 guarding glo 36  33• planned for urgent CT abdomen ALT 776  2939 – TRO pancreatitis ALP 66  131 Tot Bil 19  25 copyright to anor hidayah
  • seen back by surgeon @5pm• pt having spiking temperature CT Abdomen: Normal LFT , ALT increasing trend IMP: Acute hepatitis• transferred to medical ward @ 8.30pm copyright to anor hidayah
  • CT SCANcopyright to anor hidayah
  • Seen by medical consultant at 17/1/2013 @ 8:48• alert tachypnoeic - laboured breathing• BP 158/70 P 90 T 37.5• multiple white spot in the oral mucosa• generalised vesicular lesion with multiple erosions especially over face - worse over head, face, abdomen, upper chest• infected vesicular lesions which has crusted• multiple new vesicles noted over LL• vesicles over scrotum• bleeding over vesicles over face, patient unable to open left eyeTo treat as infected varicella zoster complicated by varicella pneumonitis with acutefulminant hepatitis with ocular involvementDM
  • Investigation trendsPh 7.288 WBC 9.5  23.2pCO2 20.4 HB 17.2  20.3pO2 82.9 PCV 50.2%  59%HCO3 9.4 plt 175  99BE -14.6 neu 77.6%  80%pro 78  72  64alb 42 39  33glo 36  33  31 PT 22.7ALT 776  2939  4473 INR 2.04ALP 66  131  267 Aptt 46.4Tot Bil 19  25  46
  • Medical plans• Start IV acyclovir 500mg stat and tds and Acyclovir cream over ruptured vesicles• Start on HFMO2 10L/min• Start IV flagyl 500mg tds for anerobic cover and cont IV rocephine• Increase IVD 6 pints / day• To consult Hepatologist copyright to anor hidayah
  • Review by OMF Review by Opthal• Multiple ulceration: • c/o unable to open RE since fever - right and left buccal mucosa a/w tearing and mild redness - Upper and lower gingival vision claims same as previous - FOM ruptured vesicles on lid - Soft palate Lid swelling (RE>LE, RE unable to open eye spontenously) minimal eye discharge conjunctiva mild injected with chemosis temporally cornea clear • Treat as BE conjunctivitis
  • Referred to Anaest @ 9:14• DXT - at 11am – HI  IV actrapid 10unit stat given IV sodium bicarbonate 100cc infusion - completed 12.15pm Send UFEME, urine ketone stat - done & seen Rpt DXT aftr 1hour, if still HI - to start insulin infusion• Repeat DXT - 18.1mmol/L copyright to anor hidayah
  • Seen by Anaesthetist @ 12:17• pt alert, conscious mildly tachypnoiec on HFMO2 able to talk in full sentences bp - 158/70 PR - 90 SpO2 - 99% dxt high lungs- clear CVS DRNM Abd soft generalised vesiculopapular rashes good urine output copyright to anor hidayah
  • medical MO review before transfer to ICU@ 14:35 concious lethargy and septic looking clinically dry already started on insulin infusion• IV vitamin K 10 mg daily• Increase IVD 8 pints copyright to anor hidayah
  • Ph 7.288  7.326 WBC 9.5  23.2  24pCO2 20.4  27.8 HB 17.2  20.3  20.1pO2 82.9  265 PCV 50.2%  59%  59.7HCO3 9.4  17.1 plt 175  99 56BE -14.6 neu 77.6%  80%pro 78  72  64  60 PT 22.7alb 42 39  33  28 INR 2.04glo 36  33  31  32 Aptt 46.4ALT 776  2939  4473  4876ALP 66  131  267  366Tot Bil 19  25  46  54Na+ 127  123  125 CK 215  1353  10537K+ 3.5  4.5  4.0 AST 604  4565  9755Creat 77 85  128 LDH 1026 3325  15834urea 4.2  5.6  10.1Cl- 98 95  90
  • 17/1/2013• @ 11:07 in medical ward:• Staph aureus – sensitive strain• @ 14:44 in ICU2:• Acenatobacter sp – sensitive strain• Eye swab – NG• BFMP – negative• Hep A – in process• Anti – mitochondrial antibody – In process copyright to anor hidayah
  • • Case transfer in from medical ward at 2.05pm accompany by staff nurse and PPK.• On high flow mask oxygen 10L/minute.• General condition of patient looks weak• conscious bp 148/80 hr 140 spo2 100% on hfmo2 lung clear cvs drnm abd distended, soft• At 3pm - ABP : 157/88mmHg Heart rate : 146/minute spo2 : 100% respiration rate : 10/minute• 3.10pm - ABP : 111/82mmHg heart rate : 158/minute spo2 : 100% respiration rate : 32/minute• Haemodinamically stable without inotrope support. copyright to anor hidayah
  • • 3pm - CVL line attempted by HO but failed then patient suddenly put up his right hand and talking irrelevantly and become aggressive, do not allow anyone to go near.• Staff nurse tried to calm down but patient become more aggressive• He pull out all the invasive lines and CBD. Patient jumped out from the bed and try to broke the window with his hand then took the cardiac table to break the window.• Patient try to jump from the window but was able to be pulled down with the help of SR, PPK, Male Nurse , 2 security guards, 2 policemen.• Then IM midazolam 3mg was given after he waas held down on the floor. Then patient become unresponsive and no spontaneous breathing copyright to anor hidayah
  • • Intubated by anaest team. – IV adrenaline 1mg x 6 ampoules ( 2 ampoule given via endotracheal and 4 ampoule via intravenous) – iv atropine 1mg – iv sodium bicarbonate 8.41% 100mg – iv calcium gluconate 1gram• CPR commenced for 40 minutes but patient unable to revive.• Cardiac monitoring shows asystole• Bp and Spo2 unrecordable. Both pupil fixed dilated and pulses not felt. copyright to anor hidayah
  • cause of death??• Sepsis secondary to Varricella pneumonia with acute hepatitis copyright to anor hidayah
  • 28yo, manNo smoker Uncontrol DM Metabolic acidosis Electrolyte derangement Fever VZV Hepatitis Multiple vesicular skin lesion No hx of VZV infection secondary bacterial before infection VZV Rhabdomyolisis Abdominal painLaboured breathing VZV pneumonia Abnormal ventilation tachypnoic Metabolic acidosis Hypoxia Hemorhagic skin Sepsis lesion Coagulopathy Arrythmias Bleeding from injection site VZV Opthalmicus Intracranial VZV encephalitis Bleed Hallucination DEATH Aggressive Acute Fulminant Hepatitis behaviour Septicaemiccopyright to anor hidayah shock
  • Factors contribute to the Incident• Underhydration in ward for the past 3 days• Delay in starting anti-viral• Failure to control blood sugar in ward• Inadequate fluid resuscitation in ward prior to transferring patient to ICU copyright to anor hidayah
  • Pathophysiology Classical Pathogen & Immune presentation response ImmuneComplications responses Management copyright to anor hidayah
  • Chicken-pox• Member of Herpesviridae• Sharing structural characteristics as a lipid envelope surrounding a nuscleocapsid with icosahendral symmetry – total diameter 180- 200nm• Centrally located DNA 125000 bp in length• little genetic variation copyright to anor hidayah
  • • Reservoir – human, no animal reservoir• Highly contageous – attack rate ~90% in seronegative individuals• Both sexes and all races – equivalent• Dermo & neutrotropic• Disease in children – well tolerated• More severe in adult, pregnant women and immunocompromised  often have hemorrhagic base copyright to anor hidayah
  • • Transmission – direct contact with the rash – Airborne respiratory droplets – vertical transmission mother to baby during pregnancyLocalize replication Seeding to at undefined site Ultimately develop reticuloendothelial (presumably the viremia system nasopharynx) copyright to anor hidayah
  • Signs and symptoms• In healthy children – the disease is generally mild• The illness usually 14–16 days after exposure – Incubation period 10-21 days• Prodromal symptoms : particularly in older children – Low-grade fever preceding skin manifestations by 1-2 D – 24-48 hr before rash • Mild abdominal pain • Mild cough and runny nose – Mild headache – malaise or irritability copyright to anor hidayah
  • Signs and symptoms• red, itchy rash appear first on the scalp, face, trunk• Diffuse and scattered nature• quickly turn into clear fluid-filled vesicles• 24-48 hr later, vesicular fluid become cloudy – recruitment of PNM leucocytes and presence of degenerated cells and debris.• Ultimately vesicle may rupture and release fluid (infectious virus) or reabsorbed• Umbilication of lesion• oropharyngeal, vagina involvement : common• cornial involvement and serious ocular disease : rare• Itching may range from mild to intense copyright to anor hidayah
  • • Vesicle involve cornium and dermis• Degenerative changes balloning, presence of multinucleated giant cells and eosinophilic intranuclear inclusion• Infection at localize blood vessels of the skin resulting in necrosis an epidermal hemorrhage copyright to anor hidayah
  • Immune response• Natural infection induces lifelong immunity• Newborn babies of immune mothers are protected by passively acquired antibodies during their first months of life copyright to anor hidayah
  • HSV• Mechanism of reactivation VZV resulting in Herpes zoster is unknown• Presumedly virus infect dorsal roots ganglia during chicken pox, remain latent until activated• Histopathologic examination  Hemorrhage, edema and lymphocytic infiltration copyright to anor hidayah
  • High-risk groups• High risks of complications – Newborns and infants whose mothers never had chickenpox or the vaccine – Teenagers & Adults – Pregnant women – People whose immune systems are impaired by another disease or condition – People who are taking steroid medications for another disease or condition, such as asthma – People with the skin inflammation eczema copyright to anor hidayah
  • COMPLICATIONS copyright to anor hidayah
  • • herpes zoster shingles • Endocarditis, myocarditis• secondary bacterial skin and • toxic shock-like syndrome soft tissue infections • hepatitis – severe invasive group A • thrombocytopenia streptococcal infection increases the risk - fold* hemorrhegic varicella• bacteremia • cerebellar ataxia• pneumonitis • encephalitis• osteomyelitis• septic arthritis• Coagulopathy, DIVC copyright to anor hidayah
  • VZV CNS infection• Aseptic meningitis and encephalitis• In many cases of aseptic meningitis – no etiology is identified – VZV has been identified as the 3rd most common cause after herpes virus and enterovirus. copyright to anor hidayah
  • Classic meningeal signs Classical Encephalitis signs• Headache • Altered level of conciousness • Confusion• neck stiffness • Behavioural abnormalities • Hallucination• Photophobia • Agitation• present with or without • Personality changes a preceding rash. • Frank psychotic state• typically have pleocytosis• elevated protein on CSF analysis• Prompt treatment with high-dose intravenous acyclovir on an empiric basis is typically the standard of care. copyright to anor hidayah
  • Varicella pneumonia• The most common and serious complication• Reported incidence in healthy adults that is 25-fold greater than in children• Varicella pneumonia is so uncommon – large-scale studies are difficult to conduct – most published studies represent either collections of small case series or retrospective analyses over many years. copyright to anor hidayah
  • • Varicella pneumonia usually presents 1–6 days after the onset of the rash – Tachypnoea – chest tightness – Cough – Dyspnoea, – Fever – Occasionally with pleuretic chest pain – haemoptysis.• Physical findings are often minimal and chest radiographs typically reveal nodular or interstitial pneumonitis• With the exception of hypoxia, physical signs are a poor guide of severity copyright to anor hidayah
  • • There is a strong correlation between pneumonia and the development of new respiratory symptoms.• increased risk in smoker• Increased number of skin spots (>100 spots), i.e. severity of rash, was a factor that increased the risk of developing pneumonia, may be a reflection of enhanced viraemia. copyright to anor hidayah
  • • The pulmonary lesions – endothelial damage in small blood vessels – with focal haemorrhagic necrosis – mononuclear infiltration of alveolar walls – fibrinous exudates with macrophages in the alveoli which contain eosinophilic intranuclear inclusions.• Seems to occur through the bloodstream rather than local extension through the respiratory tree copyright to anor hidayah
  • • Acyclovir reduces mortality and should be used early in the course of illness in patients with suspected or proven chickenpox pneumonia.• Healing with multiple nodular shadow that may be calcified copyright to anor hidayah
  • VZV ARDS• The early start of antiviral agent has been reported in a significant improvement of oxygenations as well as fever and tachypnea• Very rare• Potentially life threatening copyright to anor hidayah
  • Varicella Hepatitis• VZV hepatitis with acute liver failure – Uncommon – frequently fatal condition – The few patients who survived received early acyclovir and Liver transplant – Most of the patients described were immunocompromised copyright to anor hidayah
  • • presenting symptoms – cutaneous varicella lesions – acute abdominal or back pain – fever• The typical papulovesicular rash may precede , be concomitant with or appear delayed relative to the abdominal complaints. Patients with disseminated Varicella appear to remain moderately ill for some days and then go on to develop full-scale liver failure with coagulation disturbances and shock. copyright to anor hidayah
  • • The mechanisms  remains unclear• Most likely related more to the impaired immune function than to the virulence of the VZV strain.• Infection usually appears to be primary infection• Histopathologic examination of the liver contributes to the diagnosis copyright to anor hidayah
  • VZV Rhabdomyolysis• Elevated CK and myoglobin• Muscle damage was likely to account for some part of the elevations of AST and LDH• Very rare• Carries good prognosis• Aggressive fluid therapy to protect against renal failure copyright to anor hidayah
  • Treatment• Treatment approaches – supportive measures eg Hydration – antiviral therapy – varicella zoster immune globulin (VZIG) ( 5g/day x 5days) – management of secondary bacterial infection. – Recognize underlying co-morbid eg: DKA• Early recognition of secondary bacterial infections. Failure to recognize occult infection may result in serious illness and even death. copyright to anor hidayah
  • Acyclovir therapy• Oral 800mg 4 times /day for 5-7days• Recommended for adolecents and adults < 24 hrs of infection• More effective in HZV infection – accelerated healing of lesions, resolution of Zoster associated pain• In Severe Chickenpox infection, should be treated at the onset  reduce occurrence of visceral complications copyright to anor hidayah
  • • Penetration into CSF  Excellent ~ 50% of serum level• Complications: – Increase urea and increase creatinine ~5% – Thrombocytopenia ~ 6% – Gastrointestinal ~ 7% – Neurotoxicity ~ 1% copyright to anor hidayah
  • Varicella Vaccine• Live attenuated vaccine (Oka)• Recommended in all children > 1 yr age and seronegative adult copyright to anor hidayah
  • Varicella Immunoglobulin• special consideration in Adults – not received the vaccine – not already had chickenpox – higher risk for exposure/transmission Temporary protection of non-immune individuals can be obtained by injection of varicella-zoster immune globulin within 3 days of exposure The immunity acquired in the course of varicella prevents neither the establishment of a latent VZV infection, nor the possibility of subsequent reactivation as zoster copyright to anor hidayah
  • References• Harrison Principles of Internal Medicine, Volume 1, 17th Edition, 2008• Davidson’s Principles & Practice of Medicine, 20th Edition, 2006• Fulminant varicella Infection complicated with ARDS and DIVC in Immunocompetent Young Adult, Soshoku et al, 2004• Varicella pneumonia in adults, A.H. Mohsen*, M. McKendrick, Eur Respir J 2003; 21: 886–891• Varicella-Zoster Virus Infection Associated with Acute Liver Failure, Hilde et al, 1998 copyright to anor hidayah
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