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ICU ADMISSIONS:3214
No SIRS:766 (23.8%)
{44.9%}SIRS Without
Organ Dysfunction:1651 (51.4%)
{26.8%}
SIRS With Organ Dysfunction:
797 (24.8%){28.3%}
Due to SEPSIS:495 (62.1%)
{43.1%}Not due to SEPSIS:302 (37.9%)
{56.9%}Died In ICU:
235 / 491 (47.9%) {26.5%}
Died Within 28 Days:257 / 491 (52.3%) {32.4%}
Died In Hospital:267 / 491 (54.4%) {37.5%)
ANZICS
15.4 % of ICU admissions had SEVERE SEPSIS
MALE: 156 (66.4%)
FEMALE: 79 ( 33.6%)
ICU Mortality 47.9% 27% 30.8% - 26.5%
SMR 1.35 1.25 1.28 - 0.68
28 Days Mortality 52.3% - - - 32.4%
Hospital Mortality 54.4% 36% 44.7% 22.9% 37.5%
Med Duration Of ICU Stay (IQR)
6 days( 3 – 11 )
6.9 days(3.1-15)
4 days -6days
( 3 – 12 )
Med Duration Of Hospital Stay (IQR)
15 days( 8 – 26 )
17.8 days(8 - 38.2)
20 days11.8 days +
2.6(Mean +SD)
–
MORTALITY & MORBIDITY
ORGANISM (%) (%) (%) (%)
GRAM-POSITIVE BACTERIA 16.7 40 52.1 48.3
GRAM-NEGATIVE BACTERIA
61 38 37.6 38.5
FUNGAL 5 17 4.613.2VIRUSES &
PARASITES 17.3 1 -
INFECTIVE ORGANISM
Causes Of Deaths Of Severe SEPSIS Pts
1. Sepsis/ Multi-organ failure-unsupportable 78%
2. Sepsis/ Multi-organ failure-treatment limited or withdrawn 11.9%
3. Isolated respiratory failure 5.5%
4. Unheralded cardiac arrest 3.7%
TOTAL 100
ATTRIBUTABLE MORTALITY
Mortality all patients (ITU) – 17%
Mortality of sepsis patients (ITU) – 47.9%
SITE OF INFECTION
SITE Number SEPSIS Episodes (%)Lung 196 38.6Intra-abdominal 72 14.2Blood 108 21.3Urinary Tract 68 13.4Skin 35 6.9Gynecologic 6 1.2CNS 6 1.2Nose 2 0.4Infection Suspected But Source Unknown 61 12
Bone/Joint 2 0.4TOTAL 556 109.6
Site of infection in 508 episodes of severe sepsis in 495 patients (total >100% as more than one site of infection found in 41 episodes of sepsis).
No. of episodes where infection primary reason for admission to ICU 469 (90.2%)
No. of episodes where infection acquired after admission to ICU 58 (11.2%)
No. of SEPSIS episodes were culture positive (all cultures) 233 (46.2%)
INFECTIVE ORGANISMORGANISM NUMBER (%)
GRAM POSITIVE
MRSA 12 (3.8)Enterococcus 11 (3.5)MSSA 23 (7.3)Staph Coag Negative 1 (0.3)Viridin Streptococci 1 (0.3)Streptococci Pneu 3 (0.9)Non-haemolytic Streptococci 2 (0.6)
TOTAL 53 (16.7)
GRAM NEGATIVE
Klebsiella 46 (14.5)Pseudomonas 48 (15.1)Acinetobacter 31 (9.7)E. Coli 53 (16.7)Enterobacter 14 (4.4)Brucella 1 (0.3)Salmonella 1 (0.3)
TOTAL 194 (61)
INFECTIVE ORGANISM
ORGANISM NUMBER (%)
FUNGALCandida 9 (2.8)
Aspergillus 7 (2.2)
TOTAL 16 (5)
VIRUSES & PARASITES
Dengue 7 (2.2)
Vivax Malaria 3 (0.9)
Falciparum Malaria 45 (14.2)
TOTAL 55 (17.3)
Our Experience with Cytosorb Device atRuby Hall Clinic Hospital Pune, India
H1N1 patient with sepsis at presentation to ICU
ECMO Cytosorb ECAC CRRT
Cytosorb Used for Patients not responding to SOC oct 13‐oct 14
19 ICU patients (14 men, 5 women) aged 24‐ 72 years
Antibiotics, Vasopressors, Intravenous (IV) fluids, and sepsis dose steroids
Vasopressors administered included noradrenaline (range 0.025 ‐0.5 g/kg/min), vasopressin (range 0.5‐4 units/hr) and adrenaline (range 0.01‐0.5 g/kg/min).
SOC
IV fluids were administered as per the requirements according to SSC 2012 guide lines, and sepsis dose steroids such as hydrocortisone (50 mg IV QID) were also administered
(n=27) adjuvant therapy.ECAC
Standard of Care followed in all Patients
• Antibiotics administered included meropenam, teicoplanin, clarithromycin, doripenam, fluconazole, ulinastatin, metronidazole, caspofungin, etc were used as per appropriate indications
• Vasopressors administered included noradrenaline (0.025 ‐0.5 ug/kg/min), vasopressin (4 units/hr) IV fluids (500 to 100 mL) after adequate fluid resuscitation including normal saline (NS), Ringer lactate (RL), and sepsis dosed steroids such as corticosteroids (50mg IV QID) were also injected.
PM was >60% in 9 patients, 50% ‐ 60% in 1 patient, 40%‐50% in 5 patients, 30%‐40% in 3 patients, and <30% in 1 patient .
Overall, 4 patients survived; of the survived patients, 3 were given ECAC early, i.e., within 24 hours of admission.
Case 1
• A 62 year old elderly gentleman known hypertensive, presented with history of pain abdomen, fever high grade associated with chills and rigors and vomiting of 6 days duration
• p/H periampulary carcinoma, operated (2008/ Whipples surgery)
• He was admitted and investigated at a outside hospital and was found to have dilated CBD with ? Mass compression due to recurrent disease and shifted to us for further management
• Conscious, Oriented
• Febrile
• HR: 110/min, BP: 90/60 mm of Hg
• Per Abdomen: Mild tenderness diffuse, No rigidity, No guarding
• Admitted in the ward
• Investigated and was found to have Neutrophilic leukocytosis, deranged liver function tests
Clinical Examination at admission
• Shifted within a few hours to ICU in view of hypotension and decreased urine output
• On examination at ICU admission :
Drowsy, arousable,
Cold clammy extremities, Fever 103.4 F,
HR: 124/min, BP: 60/40mm of Hg, RR: 36/min
ABG showed Anionic gap Metabolic acidosis
APACHE II 25 , PM 34%
Standard Management SSC not enough
• Intubated, ventilated, Central line insertion, arterial line insertion for Invasive monitoring, fluid resusc
• Blood, Urine, Tracheal cultures sent
• Antibiotics: , Inj piperacillin tazobactum 4.5gm IV tds, changed to
Inj Meropenem 1gm IV TDS & Inj Teicoplanin 400mg Bd f/b 200mg IV OD,
• Inj Hydrocortisone 50mg IV QID
• Inj Ulinastatin 1mu BD
• Cytosorb Filtration for six hours
• Parenteral Nutrition
32
Cytosorb Treatment Patient underwent a 6 hour cytosorb filtration after stabilisation with Inotropes on day 1 of admission to ICU
LAB PARAMETE
RS
18/8Ward
19/8ICU
20/8Cytosorbtherapy
Ulinastatin
21/8 22/8CRRT 23/8
24/3Second cytosorbtherapy
Hb 12.5 10.4 8.1 8 8WBC 12700 31100 42800 37800 37700
N’phils 97.8 92.7 96 96.2 87.8Platelets 117 30 20 15 25Bl. Urea 55 123 220 245 181Sr. creat 1.9 4 5.1 5.5 3.9Bilirubin 6.8 7.6 2.9Direct 3.9 4.4 2.1ALT 180 225 66AST 218 362 94
Alk Po4 439 481 173Total Protein 6.5 5.1 4.8Albumin 3.3 2.2 2.3Lactates 8.8 4Hs rCp 22.8 8
Ammonia 2.7
Urine and blood cultures showed ESBL E.coli sensitive to Ertapenem, Imipenem, Meropenem and Amikacin confirming the final diagnosis of urosepsis
Follow up treatment
• Patient required one more cytosorb therapy and alternate day hemodialysis for acute renal failure
• Extubated on day 8,
• Patient is Afebrile, on room air in a hemodynamically stable condition
• And discharged home
• Follows up for last 3 months regularly and is well
• A 28 yr old male, no known comorbidities except h/o surgery for Rt ureteric calculus in July 2013,non alcoholic presents to the casualty room with C/O
sudden onset of pain in abdomen, severe pain, diffuse in nature, radiating to back, intense in supine position, relieved in sitting position
nausea & 4 e/o vomiting containing food particles, non projectile in nature since last 2 days
Breathlessness since 1 day
Presenting Complaints
• No c/o constipation, fever, hematemesis/malena, chest pain, breathlessness, dysuria, no pedal edema
• He was admitted in another hospital where USG was done s/o a 7mm calculus in the left kidney with moderate free fluid and distended gall bladder with diffuse probe tenderness.
Outside Investigations 13/8
Hb/ Hct 20.7/ 67.8WBC 25200
N’phils 85%Platelets 278Bl. Urea 56Sr. creat 1.1Bilirubin 1.1
Direct 0.6ALT 56AST 59
Amylase 925
LAB PARAMETERS before Admission
Clinical Examination on Admission
• Conscious, Oriented but restless• Temp : 99.8 F, periphery cold • HR : 130/min, sinus tachycardia, BP : 84/50 mm of Hg & RR : 30‐35/min, SpO2 : 88% on V.Mask with 50% FiO2
• No pallor/icterus/edema• P/A :Distention, diffuse Tenderness +, tympanic note on percussion, bowel sounds diminished
• RS : B/L basal crepts on auscultation• CVS & CNS : NAD
DDs Of Acute Abdomen in this case
1. Acute pancreatitis2. Acute Appendicitis3. Perforation4. Renal colic5. Mesenteric vascular occlusion6. Diabetic ketoacidosis
LAB INVESTIGATIONS
• Hemogram: WBC count 20,400, 86% Neutrophills,HB 15.8gm%,Hematocrit 52%
• LFT : T. Bilirubin 1.4, AST 54 U/L, ALT 60 U/L, Alk Po4,albumin WNL
• PT,INR WNL
• Sr urea mildly raised, creatinine, Sr Electrolytes WNL
• Sr amylase & Lipase levels: 1007 U/L & 2853 U/L respectively
• Sr Calcium 14 mg/dL,Sr Magnesium 1.7 mg/dL,Random BSL 180 mg/dL
• ABG : Metabolic acidosis, pH :7.25,HCO3 14,PCO2 :30mm Hg, PaO2:60mm Hg on 50% FiO2
• Lactates :4.4 mmol/l & C reactive protein level : 32.4 U/L
LAB INVESTIGATIONS• Sr Triglycerides level WNL• Urine routine :WNL, 12 Lead ECG : WNL• S calcium 14 mg/dl• Radiology : still non conclusive and patient deteriorating CT planned
• CXR : B/L moderate pleural effusion
• X ray erect abdomen : No air fluid levels
• USG : Liver, GB & CBD normal, sludge within GB, pancreas obscured by gas shadows, mild ascites, no evidence of renal calculi or hydronephrosis
• 2 D Echo : EF :55%,No RWMA, IVC not full & collapsible
Suspected pancreatitis .. COURSE IN ICU .. • ABC Management
• I/v/o Tachypnea, hypoxia & hemodynamic instability, pt was intubated & mechanical ventilation started
• Rt IJV triple lumen ,RT& Foley’s catheter inserted: ‐ CVP was 7 mm Hg, urine output 50‐60ml/hr, concentrated
• IV Fluids : 1000 mL RL was given as bolus, in 24 hrs required total 5 liters of crystalloids
• Required Noradrenaline support
Management
• Analgesics :Inj Tramadol 75 mg iv TDS
• Inj Pantoprazole 40 mg OD & Inj Ondansetron 4mg iv TDS
• Inj Octreotide 100 mcg S/C TDS started
• Inj meropenem 1gm iv TDS started
• CECT abdomen was done after fluid resuscitation. N –acetyl cysteine 600mg was given before & after contrast administration.
Course in the ICU deteriorating • On day 2,even after vigorous fluid resuscitation, he was having tachycardia of 150‐160 bpm, hypotension requiring noradrenaline support
• He had fever spikes 103 F,5‐6 e/o fever spikes in a day
• His WBC,CRP & Procalcitonin levels were high
• Treatment for Hypercalcemia started with Salmon calcitonin spray & IV fluids
• Nutritional support was given through RT feeds from Day3
CYTOSORB TREATMENT
Decision was taken to start extracorporeal purification session ,Rt femoral HD canulainserted
Total 3 extracorporeal purification sessions were done each for 6 hrs on day2,4&6
PTH levels confirmed to be very high
Patient had grown Acinetobacter baumanni in Endotracheal tube and Dialysis lumen tip
Tigecycline was started accordinng to sensitivity report
Serial USG was done which shows minimal peripancreatic collection and mild ascites
Febrile spikes decreased after 7 days
Pt was extubated on day 8 after weaning trial
HD canula was removed
Oral feeds were started from day 10
Treatment Course following CYTOSORB
2014 14/8 15/8 16/8 18/8 19/8 21/8 22/8Hb 12.9 13.1 13.1 11 10.1 10.4 11.4
WBC 20400 14800 24800 14100 23100 17100 13900N’phils 86 76 76 78 86 83 89.8Platelets 174 179 169 219 246 312 284Bl. Urea 70Sr. creat 1.4 1.5Lipase 2853 867
Amylase 1007 543Na 134 139K 4.8 4.5
Ca 14 11.2 13.4 14 11.7 9Mg 1.7
HsCrp 32.4 23.7 10.9 7.9PTH 386.3
Lactate 4.4 2.8
Follow UP• Since PTH levels were found high
• Initially USG neck & subsequently radionucleotide scan was done which suggested Parathyroid adenoma
• Inj Tigecycline was continued for total 14days
• Pt was shifted from ICU to ward on day 11 & got discharged from hospital after 14 days
• He was adviced Sx for adenoma
• A 40 year old housewife (no co‐morbidities, non obese) presented with chief complaints of
Cough with expectoration, Sore throat, Fever since 2 days
• She went to General practitioner who treated her with paracetamol, cough syrup, oral antibiotic and Prednisolone
Her symptoms however deteriorated & she developed breathlessness 4 days later and she was referred to us.
Clinical Examination on Admission
• O/E:Conscious, restlessFebrile , axillary temperature 101 F, warm peripheryHR : 104/min, Sinus tachycardia, BP : 104/60 mm HgRR: 35‐40/min,SpO2 :80% on Room air & 89% on V. Mask with 50% FiO2ABG ‐moderate hypoxemia with increased alveolar arterial gradientSerum lactate ‐ 4.7 meq/L
• Standard of care therapy given as SSC • Blood ,urine & sputum cultures sent
• Initially, IV fluids were given by 2 large bore peripheral IV lines
• Inj Levofloxacin 500 mg iv, Inj piperacillintazobactum 4,5 gm iv, Tab doxy 100 mg, Tab Oseltamivir 150 mg BD
• CVP was maintained between 10 ‐ 12 cm of water with IV Crystalloids.
• MAP maintained > 70 mm Hg without inotropes
Treatment continued…….• NIV BiPAP for 2 hours, 60% FiO2, SpO2 above 90% RR high
• CXR showing B/L lung infiltrates• Suspected viral / seasonal influenza pneumonia
• ABG 2 hours later, shows worsening of hypoxemia,
• P:F ratio 90 and CO2 55
• Intubated and ventilated, 80% FiO2 & PEEP of 8
• Poor lung compliance, required Pressure control mode with
• 100% FiO2,PEEP from 8 to 13 cm H2O,Pressure above PEEP from 16 to 20 cm H20, SpO2 was 85‐88%,plateau pressure (Ppl) ,30 cm H2O, PCO2 : 60 mm Hg
worsening over 24 hrsH1N1 positive
• Patient worsened gradually with worsening hypoxia,PaCO2 ‐ 119 mm Hg
• Prone ventilation for 12 hours, pCO2 came down to 71 mm Hg
• APACHE 25, predicted mortality 60%
• Hemodynamically unstable requiring high ionotropes• Subsequently she landed in acute renal failure despite adequate preload & MAP with inotropes, started on CRRT
• Cardiac output (CO),SVV,DO2,VO2 was monitored using Vigilio monitor• Cytosorb filter therapy was initiated on day 2 repeated on 3rd and 5th day
• Her throat swab returned positive for H1N1
Date / ECAC 16/8/14 / I 17/8/14 / II 18/8/14 19/8/14 / III 22/8/14
Hb 12.5 10.4 7.9WBC 6100 17800 34700
N’phils 90.4 83.3 88Platelets 234 145 112Bl. Urea 51 81 91Sr. creat 0.7 2,2 4.8
T.Bilirubin/D.bil 0.3/ 0.2 1.2/1.1ALT 20 18AST 46 88
Alk Po4 241 102
Total Protein / alb 6.5/ 2.6 /3.3
Hs rCp 21.3Lactate 7
Lactates 4.5 2.7
Hba1c 13.09
Follow Up Treatment … lost her • On 21/8 morning, her CXR ,P:F ratio showing improvement however she was requiring maximum ionotrpic support
• Ventilator requirement were reduced in terms of pressure above PEEP ,lung compliance was improved little bit as on loops but was on PC 100% FiO2 & PEEP of 14
• Antibiotics were stepped up to meropenam & colistin
• On 22/8, however her P:F ratio detoriated,pCO2 started rising, ABG showing severe respiratory & metabolic acidosis,pH 6.8,pCO2 92,HCO3 8,pO2 36 on 100% FiO2
• Possibility of pneumothorax & pulmonary embolism was ruled out with CXR,2D echo & USG thorax
• Subsequently she went into cardiac arrest & could not be revived
• Cause of death : H1N1 pneumonia with septic shock with multiorgan failure
Case Presentation
• A 58yr old male patient, known case of hypertension was brought by relatives with c/o
• severe breathlessness• fever and cough since last 3‐4days
• Patient desaturated and near resp arrest in the causality hence was intubated and ventilated
Clinical Examination on Admission .. Near resp arrest
Afebrile/unconscious
HR 78/min … developing brady , BP 90/50mm Hg
SPO2 28% in casualty
CVS S1S2 heard
RS air entry decreased on left side.B/L fine crepts +
P/A soft,non tender
CNS E3M3Vt
Patient was shifted to ICU and was started on ionotropic support of Noradrenaline and midaz infusion and on high ventilator support
Day 1Lab Parameters• HB 10.6, WBC 4700, PLATELETS 1.6LAC
• LACTATE 10.9• LDH 5600U/L• CRP 102mg/L• urea 28.4, creatinine 1.1• ALT 16,AST 71
• CXR S/o homogenous opacity in b/l perihilar region sparing b/l apical and lower lobes represent pulmonary edema.
• 2d echo was done S/O LVEF 60%,PA pressures 47mm hg
Treatment Initiated• Antibiotics Inj.meropenum 1gm 8hrly• Inj.Targocid 400mg once a day• Inj.levof;ox 500mg once a day • Cap fluvir 75mg twice a day was started with other supportive medications.
CYTOSORB THERAPY• Cytosorb therapy over 8hrs was advised seeing clinical condition of patient.
DAY 2• Lab Parameters after cytosorb therapyWBC 6200
HB 9.1
PLATELETS 1.5LAC
LACTATE 1.7
CRP 76.63
Urea 34.9, creatinine 0.7
Clinical improvement markedly seen
CXR B/L lung fields show homogenous opacities, left CP angle obscured ?pleural effusion.(SLIGHT IMPROVEMENT SEEN.)
DAY 3
H1N1 SWAB WAS SENT & REPORT WAS NEGATIVE
NEGATIVE FOR DENGUE,CHIKENGUNYA,WEST NIL VIRUS, PLASMODIUM SPP, LEPTOSPIRA SPP, SALMONELLA SPP.
INFLUENZA A WAS DETECTED
2ND SESSION of Cytosorb device therapy was initiated
• Day 4Lab Parameters after 2nd session of Cytosorb therapy
• WBC 9400
• HB 8.3g
• PLATELETS 1.62LAC
• CRP 12.73mg/L
• Urea 74.7,Creatinine 0.8
CXRS/O homogenous haziness in left lower zone with blunting of CP angle s/o pleural effusion. In homogenous radiopacicty seen scattered in both lungs s/o alveolar opacification
CRP Before and After Cytosorb therapy
108
12,73
0
20
40
60
80
100
120
Before After
CRP
mg/dl
Achsentitel
Diagrammtitel
DAY 5• Patient off ionotropic supports • WBC 9400• HB 8.3g• PLATELET COUNTS 1.62LAC• Urea 57.8, creatinine 0.7
• PATIENT IMPROVING CLINICALLY.
CONCLUSIONS: THE CYTOKINIC APPROACH IS COMPLEMENTARY
TO THE CYTOTOXIC APPROACH
• Although challenging,• this new theory can be considered complementary to the existing cytotoxic hypotheses by coupling reduced endothelial damage at the interstitial level (cytotoxic approach)
• with the concept of reprogramming leucocytes and mediators toward infected tissue,
• thus emptying the bloodstream of important promoters of remote organ damage (cytokinic approach).
• In this context,• optimal device development and• better estimation of timing, dose and targets
• are mandatory before embarking onlarge randomized studies to assess morbidity and mortality issues.
Moving from a Cytotoxic to a Cytokinic Approach in the Blood Purification Labyrinth: Have We Finally Found Ariadne’s Thread?Patrick M Honore, et all doi: 10.2119/molmed.2012.00300
Advances in immunology and our understanding of the pathophysiological basis of sepsis provide exciting new therapeutic opportunities
Sepsis and septic shock are among the leading causes of death in intensive care units worldwideCytokines which may have crucial role in the complex pathophysiology underlying sepsis may dysregulate the immune response and promote tissue‐damaging inflammation.
With Current Treatment modalities in Sepsis Management the mortality is high
Extracorporeal therapies like Cytosorb provides window of opportunity to doctors to manage Sepsis .. Who .. when ..how much… needs to be answered .
To conclude……..
Thank you
In this context optimal device development andbetter estimation of timing, dose and targetsare mandatory before embarking onlarge randomized
studies to assess morbidity and
mortality issues.
Moving from a Cytotoxic to a Cytokinic Approach in the Blood Purification Labyrinth: Have We Finally Found Ariadne’s Thread?Patrick M Honore, et all