Mortality review on Fulminant Varicella Infection

copyright to anor hidayah

Mortality Review(January 2013)

Dr Nor Hidayah Zainool AbidinINTERNATIONAL ISLAMIC UNIVERSITY OF MALAYSIA

HOSPITAL SULTAN ABDUL HALIM

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

painRash then spread to face, trunk and bilateral upper limbs and going downwardsNow involved bilateral lower limbs

• Also having mild URTI symptoms - coughNo 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



Examination in Yellow Zone

• alert ,pinknot tachypnoiechydration goodlungs: clearabdomen: soft , non tender

• Noted vesicular rash over the skull , abdomen , upper limbs• BP:134/78

SpO2: 100% under room airP:86Temp:37.4

• DXT :16.2• ECG: normal SR

• Initially treated as GERD• IV ranitidine 50mg STAT

Syrup MMT 30 ml STATIV 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


30 mins later in Yellow zone

• still having upper abdominal pain more on right hypochondriac pain

• alert ,pinknot tachypnoiecbp:147/71pr:64temp:37.6dxt:12.6

• TAS done in ED : Gallbladder stone ?

Treat as Cholitihiasiscopyright 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


Seen by surgical MO 3 hours later

• Normal vital signs• Tender epigastric

• NR for hepatitis B, hepatitis C virus and RVD

• planned for US urgent cm thus KNBMIV pantoprazole 40mg BD

treated with IM pethidine 75mg PRN• then given IM pethidine 100mg stat

– in the morning as pt still having abdominal pain

pro 78

alb 42

glo 36

ALT 776

ALP 66

Tot Bil 19


15/1/2013 @ 7:27 am• alert , concious

not tachypneic

BP: 125/76PR:71T : 37.4Sp02 : 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 livercopyright to anor hidayah


seen by medical MO @ 6:30pm

• o/e alert, concious, not tachypnoeicBP:152/88HR:81SPO2: 100T:38

• Lungs: clearCVS: DRNMAbdomen soft, non-tender, liver palpable 2 FB+ maculopapular rash on face trunk and backblanches, no discharges

• Treated with IVD 4 pints normal saline over 24 hoursCover 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

Amylase 71

Diastase 373


Seen by surgeon 16/1/2013 @ 9:15• Having pain over the back

No vomiting mild abdominal pain

alertconsciousBP:151/85P:88T:38SpO2:99

Abdomen:soft, tender on deep palpationguarding

• planned for urgent CT abdomen– TRO pancreatitis

Na+ 127 123 CK 215 1353

K+ 3.5 4.5 AST 604 4565

Creat 77 85 LDH 1026 3325

urea 4.2 5.6

Cl- 98 95

pro 78 72alb 42 39glo 36 33ALT 776 2939ALP 66 131Tot Bil 19 25


seen back by surgeon @5pm

• pt having spiking temperature

CT Abdomen: NormalLFT , ALT increasing trend

IMP: Acute hepatitis• transferred to medical ward @ 8.30pm

CT SCAN


Seen by medical consultant at 17/1/2013 @ 8:48

• alerttachypnoeic - laboured breathing

• BP 158/70P 90T 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 acute fulminant hepatitis with ocular involvementDM


Investigation trends

pro 78 72 64alb 42 39 33glo 36 33 31ALT 776 2939 4473ALP 66 131 267Tot Bil 19 25 46

Ph 7.288

pCO2 20.4

pO2 82.9

HCO3 9.4

BE -14.6

WBC 9.5 23.2

HB 17.2 20.3

PCV 50.2% 59%

plt 175 99

neu 77.6% 80%

PT 22.7

INR 2.04

Aptt 46.4


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


Review by OMF •Multiple ulceration:

- right and left buccal mucosa- Upper and lower gingival- FOM- Soft palate

Review by Opthal•c/o unable to open RE since fever

a/w tearing and mild rednessvision claims same as previous ruptured vesicles on lid Lid swelling (RE>LE, RE unable to open eye spontenously) minimal eye dischargeconjunctiva mild injected with chemosis temporally cornea clear

•Treat as BE conjunctivitis


• DXT - at 11am – HI IV actrapid 10unit stat givenIV 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

Referred to Anaest @ 9:14


Seen by Anaesthetist @ 12:17• pt alert, conscious

mildly tachypnoiecon HFMO2able to talk in full sentences

bp - 158/70PR - 90SpO2 - 99%dxt high

lungs- clearCVS DRNMAbd soft

generalised vesiculopapular rashes

good urine output


medical MO review before transfer to ICU@ 14:35

conciouslethargy and septic lookingclinically dryalready started on insulin infusion

• IV vitamin K 10 mg daily• Increase IVD 8 pints


pro 78 72 64 60alb 42 39 33 28glo 36 33 31 32ALT 776 2939 4473 4876ALP 66 131 267 366Tot Bil 19 25 46 54

WBC 9.5 23.2 24

HB 17.2 20.3 20.1

PCV 50.2% 59% 59.7

plt 175 99 56

neu 77.6% 80%

PT 22.7

INR 2.04

Aptt 46.4

Ph 7.288 7.326pCO2 20.4 27.8pO2 82.9 265HCO3 9.4 17.1BE -14.6

Na+ 127 123 125 CK 215 1353 10537

K+ 3.5 4.5 4.0 AST 604 4565 9755

Creat 77 85 128 LDH 1026 3325 15834

urea 4.2 5.6 10.1

Cl- 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



• 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 148/80hr 140 spo2 100% on hfmo2lung clearcvs drnmabd 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.


• 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


• 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.

cause of death??

• Sepsis secondary to Varricella pneumonia with acute hepatitis



Uncontrol DM Metabolic acidosis Electrolyte derangement28yo, manNo smoker

FeverMultiple vesicular skin

lesionNo hx of VZV infection

beforeAbdominal pain

VZV Hepatitis

VZV pneumonia Abnormal ventilation

Coagulopathy

HallucinationAggressive behaviour

VZV Rhabdomyolisis

VZV encephalitis

Laboured breathingtachypnoic

Septicaemic shock

Metabolic acidosis

Hemorhagic skin lesion

Bleeding from injection site

DEATH

Intracranial Bleed

Arrythmias

Hypoxia

VZV Opthalmicus

secondary bacterial infection

Sepsis

Acute Fulminant Hepatitis


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


Pathogen

Pathophysiology& Immune response

ManagementImmune responses

Classical presentation

Complications

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



• 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


• Transmission– direct contact with the rash – Airborne respiratory droplets – vertical transmission (mother to baby) during pregnancy

Localize replication at undefined site (presumably the

nasopharynx)

Seeding to reticuloendothelial

system

Ultimately develop viremia


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

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



• 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


Immune response

• Natural infection induces lifelong immunity• Newborn babies of immune mothers are protected by

passively acquired antibodies during their first months of life


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


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


COMPLICATIONS


• herpes zoster (shingles) • secondary bacterial skin and

soft tissue infections– severe invasive group A

streptococcal infection increases the risk 40-60 fold*

• bacteremia, • pneumonitis • osteomyelitis • septic arthritis • Coagulopathy, DIVC

• Endocarditis, myocarditis• toxic shock-like syndrome • hepatitis • thrombocytopenia

hemorrhegic varicella• cerebellar ataxia• encephalitis


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.


Classic meningeal signs

•Headache•neck stiffness•Photophobia•present with or without a

preceding rash.

Classical Encephalitis signs

•Altered level of conciousness• Confusion• Behavioural abnormalities• Hallucination• Agitation• Personality changes• 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.


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.


• 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


• 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.


• 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


• 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


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


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


• 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.


• 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


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


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.


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


• Penetration into CSF Excellent ~ 50% of serum level

• Complications:– Increase urea and increase creatinine ~5% – Thrombocytopenia ~ 6%– Gastrointestinal ~ 7%– Neurotoxicity ~ 1%


Varicella Vaccine

• Live attenuated vaccine (Oka)• Recommended in all children > 1 yr age and

seronegative adult


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.


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


Thank You….

Happy Chinese New Year

Mortality review on Fulminant Varicella Infection

Health & Medicine

Transcript of Mortality review on Fulminant Varicella Infection