Download Case report

1st International Cytosorb Users meet DR. PRACHEE SATHE
Director ICU Ruby Hall Clinic Pune
India Sepsis: Magnitude of problem
Indian Intensive Care Case Mix and Practice Patterns Study (INDICAPS STUDY)
ICU ADMISSIONS:
3214
No SIRS:
766 (23.8%)
{44.9%}
SIRS Without
Organ Dysfunction:
1651 (51.4%)
{26.8%}
Not due to SEPSIS:
302 (37.9%)
{56.9%}
MALE: 156 (66.4%)
FEMALE: 79 ( 33.6%)
15.4 % of ICU admissions had SEVERE SEPSIS
SIRS With
Organ Dysfunction:
797 (24.8%)
{28.3%}
Due to SEPSIS:
495 (62.1%)
{43.1%}
ANZICS
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%)
EPIDEMIOLOGY OF SEVERE SEPSIS IN INDIA
INCIDENCE OF SEVERE SEPSIS
INDIA
US
15.4%
13%
ANZICS
11.8%
UK
SOAP
27%
37.4%
MORTALITY & MORBIDITY
ICU Mortality
47.9%
27%
30.8%
-
26.5%
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 days
11.8 days +
2.6
(Mean +SD)
–
SMR
INFECTIVE ORGANISM
ORGANISM
GRAM-POSITIVE
BACTERIA
(%)
(%)
(%)
(%)
16.7
40
52.1
48.3
GRAMNEGATIVE
BACTERIA
61
38
37.6
38.5
FUNGAL
5
17
4.6
VIRUSES &
PARASITES
17.3
1
-
13.2
Causes Of Deaths Of Severe SEPSIS Pts
1.
Sepsis/ Multi-organ failureunsupportable
2.
Sepsis/ Multi-organ failure-treatment
limited or withdrawn
11.9%
3.
Isolated respiratory failure
5.5%
4.
Unheralded cardiac arrest
3.7%
TOTAL
78%
100
ATTRIBUTABLE MORTALITY
Mortality all patients (ITU) – 17%
Mortality of sepsis patients (ITU) – 47.9%
SITE OF INFECTION
Number
SEPSIS Episodes (%)
Lung
196
38.6
Intra-abdominal
72
14.2
Blood
108
21.3
Urinary Tract
68
13.4
Skin
35
6.9
Gynecologic
6
1.2
CNS
6
1.2
Nose
2
0.4
Infection Suspected But Source
Unknown
61
12
Bone/Joint
2
0.4
556
109.6
SITE
TOTAL
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
No. of episodes where infection
acquired after admission to ICU
No. of SEPSIS episodes were culture
positive (all cultures)
469 (90.2%)
58 (11.2%)
233 (46.2%)
INFECTIVE ORGANISM
ORGANISM
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
GRAM NEGATIVE
TOTAL
NUMBER (%)
53 (16.7)
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)
194 (61)
INFECTIVE ORGANISM
ORGANISM
FUNGAL
Candida
9 (2.8)
Aspergillus
7 (2.2)
TOTAL
VIRUSES & PARASITES
16 (5)
Dengue
7 (2.2)
Vivax Malaria
3 (0.9)
Falciparum Malaria
TOTAL
NUMBER (%)
45 (14.2)
55 (17.3)
Our Experience with Cytosorb Device at
Ruby 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) SOC
Antibiotics, Vasopressors, Intravenous (IV) fluids, and sepsis dose steroids
aged 24‐ 72 years 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).
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 ECAC
(n=27) adjuvant therapy.
Demographic data of our Patients on Cytosorb
APACHE score before & after Cytosorb therapy SOFA score before & after Cytosorb therapy 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.
APACHE II score and predicted mortality (PM)
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. Early & Late use of Cytosorb in patients
6 died and 3 survived Case Studies 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
Clinical Examination at admission
• 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
•
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%
Mottling of skin
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
Cytosorb Treatment Patient underwent a 6 hour cytosorb filtration after stabilisation with Inotropes on day 1 of admission to ICU
32
LAB PARAMETE
RS
18/8
Ward 19/8
ICU
Hb
12.5
WBC
20/8
Cytosorb
therapy Ulinastatin
21/8
22/8
CRRT
23/8
10.4
8.1
8
8
12700
31100
42800
37800
37700
N’phils
97.8
92.7
96
96.2
87.8
Platelets
117
30
20
15
25
Bl. Urea
55
123
220
245
181
Sr. creat
1.9
4
5.1
5.5
3.9
Bilirubin
6.8
7.6
2.9
Direct
3.9
4.4
2.1
ALT
180
225
66
AST
218
362
94
Alk Po4
439
481
173
Total Protein
6.5
5.1
4.8
Albumin
3.3
2.2
2.3
Lactates
8.8
4
Hs rCp
22.8
8
Ammonia
2.7
24/3
Second cytosorb
therapy Day 1 increasing vasopressors
Hemodynamics Post Cytosorb
Filtration Inotropes tapered off
Cytosorb & Vasopressors Dosing
WBC count in relation to Cytosorb filtration
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
CASE 2
Presenting Complaints
• 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
• 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.
LAB PARAMETERS before Admission
Outside Investigations
13/8
Hb/ Hct
20.7/ 67.8
WBC
25200
N’phils
Platelets
Bl. Urea
Sr. creat
Bilirubin
Direct
ALT
AST
85%
278
56
1.1
1.1
0.6
56
59
Amylase
925
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.
2.
3.
4.
5.
6.
Acute pancreatitis
Acute Appendicitis
Perforation
Renal colic
Mesenteric vascular occlusion
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. CT SCAN OF ABDOMEN N
CT abdomen 14/8/14
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 canula
inserted
Total 3 extracorporeal purification sessions were done each for 6 hrs on day2,4&6
Treatment Course following CYTOSORB
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
2014
14/8
15/8
16/8
18/8
19/8
21/8
22/8
Hb
WBC
N’phils
Platelets
Bl. Urea
Sr. creat
12.9
20400
86
174
70
1.4
13.1
14800
76
179
13.1
24800
76
169
11
14100
78
219
10.1
23100
86
246
10.4
17100
83
312
11.4
13900
89.8
284
Lipase
Amylase
2853
1007
Na
K
134
4.8
Ca
14
Mg
1.7
HsCrp
32.4
23.7
PTH
386.3
4.4
2.8
Lactate
1.5
867
543
139
4.5
11.2
13.4
14
10.9
11.7
9
7.9
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
Case 3
• 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
• Standard of care therapy given as SSC • O/E:
Conscious, restless
Febrile , axillary temperature 101 F, warm periphery
HR : 104/min, Sinus tachycardia, BP : 104/60 mm Hg
RR: 35‐40/min,SpO2 :80% on Room air & 89% on V. Mask with 50% FiO2
ABG ‐ moderate hypoxemia with increased alveolar arterial gradient
Serum lactate ‐ 4.7 meq/L • Blood ,urine & sputum cultures sent
• Initially, IV fluids were given by 2 large bore peripheral IV lines
• Inj Levofloxacin 500 mg iv, Inj piperacillin
tazobactum 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 hrs
H1N1 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
Hb
WBC
N’phils
Platelets
Bl. Urea
Sr. creat
T.Bilirubin/D.bil
ALT
AST
Alk Po4
12.5
6100
90.4
234
51
0.7
0.3/ 0.2
20
46
241
Total Protein / alb
6.5/ 2.6
Hs rCp
21.3
Lactate 7
Hba1c
13.09
17/8/14 / II
18/8/14
10.4
17800
83.3
145
81
2,2
19/8/14 / III
22/8/14
7.9
34700
88
112
91
4.8
1.2/1.1
18
88
102
/3.3
Lactates 4.5
2.7
Cytosorb device in the ECT circuit
Day 1
Day 6
Day 4
Day 9
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 4
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 1
Lab 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 therapy
WBC 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 4
Lab 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
Diagrammtitel
120
108
100
mg/dl
80
60
40
20
12,73
0
Before
After
CRP
Achsentitel
DAY 5
•
•
•
•
•
Patient off ionotropic supports WBC 9400
HB 8.3g
PLATELET COUNTS 1.62LAC
Urea 57.8, creatinine 0.7
• PATIENT IMPROVING CLINICALLY.
H1N1 and Severe septic shock in a young man : ECMO ,ECAC , CRRT 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 on
large 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
To conclude……..
Sepsis and septic shock are among the leading causes of death in intensive care units worldwide
Cytokines 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 Advances in immunology and our understanding of the pathophysiological basis of sepsis provide exciting new therapeutic opportunities
Extracorporeal therapies like Cytosorb provides window of opportunity to doctors to manage Sepsis .. Who .. when ..how much… needs to be answered .
In this context optimal device development and
better estimation of timing, dose and targets
are mandatory before embarking on
large 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 Thank you