Therapeutic Plasma Exchange as Rescue Therapy in Severe Sepsis and Septic Shock

Retrospective Observational Single-Centre Study of 23 Patients

Johannes Hadem; Carsten Hafer; Andrea S Schneider; Olaf Wiesner; Gernot Beutel; Thomas Fuehner; Tobias Welte; Marius M Hoeper; Jan T Kielstein

Disclosures

BMC Anesthesiol. 2014;14(24)

Abstract and Introduction

Abstract

Background: Several case series and small randomized controlled trials suggest that therapeutic plasma exchange (TPE) improves coagulation, hemodynamics and possibly survival in severe sepsis. However, the exact role of TPE in modern sepsis therapy remains unclear.

Methods: We performed a retrospective observational single-centre study on the use of TPE as rescue therapy in 23 consecutive patients with severe sepsis or septic shock from 2005 to 2012. Main surrogate markers of multiple organ failure (MOF) before, during and after TPE as well as survival rates are reported.

Results: At baseline, mean SOFA score was 13 (standard deviation [SD] 4) and median number of failed organ-systems was 5 (interquartile range [IQR] 4–5). TPEs were performed 3 days (IQR 2–10) after symptom onset and 1 day (IQR 0–8) after ICU admission. The median total exchange volume was 3750 ml (IQR 2500–6000), which corresponded to a mean of 1.5 times (SD 0.9) the individual plasma volume. Fresh frozen plasma was used in all but one treatments as replacement fluid. Net fluid balance decreased significantly within 12 hrs following the first TPE procedure by a median of 720 mL (p = 0.002), irrespective of outcome. Reductions of norepinephrine dose and improvement in cardiac index were observed in individual survivors, but this was not significant for the overall cohort (p = 0.574). Platelet counts decreased irrespective of outcome between days 0 and 2 (p < 0.003), and increased thereafter in many survivors. There was a non-significant trend towards younger age and higher procalcitonin levels among survivors. Nine out of 23 TPE treated patients (39%) survived until ICU discharge (among them 3 patients with baseline SOFA scores of 15, 17, and 20).

Conclusions: Our data suggest that some patients with severe sepsis and septic shock may experience hemodynamic stabilisation by early TPE therapy.

1 2 3 4 5 6

Next Section

Abstract and Introduction
Background
Methods
Results
Discussion
Conclusion
References

Table 1. Septic focus, associated pathogen(s) and risk factors for infection
Patient	Septic focus and associated pathogen(s)	Risk factors for infection
1	Septic shock (pneumonia, Staphylococcus aureus)	Microscopic polyangiits, cryoglobulinemia, chronic renal disease
2	Severe sepsis (soft tissue infection, Streptococcus pyogenes)	None
3	Septic shock	Pancytopenia, cryoglobulinemia
4	Septic shock (perianal soft tissue infection, Streptococcus group A)	Excision of an anal tag
5	Septic shock (pneumonia, Pseudomonas aeruginosa)	UIP, Sjögren's syndrome, alveolitis, immune complex vasculitis
6	Septic shock (parastomal abscess, Peptostreptococcus, Candida) with septic or Infliximab-associated cardiomyopathy	Crohn's disease with anal and parastomal fistulas
7	Septic shock (pneumonia, Streptococcus pneumoniae)	Post splenectomy
8	Septic shock (pneumonia, Escherichia coli)	None
9	Septic shock	Crohn's disease, short bowel syndrome
10	Severe sepsis (rhabdomyolysis and pneumonia, Adenovirus, Streptococcus pneumoniae, Staphylococcus aureus)	None
11	Severe sepsis (pneumonia, H1N1) with VAHS	Type 2 Diabetes, obesity hypoventilation syndrome
12	Septic shock (pneumonia, Staphylococcus haemolyticus, Candida krusei)	MDS with pancytopenia
13	Severe sepsis (pneumonia, H1N1, Strepococcus mitis, Serratia marcescens) with VAHS	None
14	Severe sepsis (pneumonia)	MDS, secondary AML, PBSCTx
15	Septic shock, OPSI (sinusitis, Streptococcus pneumoniae)	Post splenectomy
16	Septic shock (pneumonia, Staphylococcus aureus)	Cystic fibrosis, re-double-lung transplantation, diabetes, liver cirrhosis
17	Septic shock (pneumonia, Streptococcus pneumoniae)	Multiple myeloma, AL amyloidosis (cardiac, renal), autologous SCTx 4 months ago,
18	Septic shock (pneumonia)	Septic granulomatosis
19	Septic shock, OPSI (chronic otitis, Streptococcus pneumoniae)	Kidney transplantation, rapidly progressive GN, s/p acute rejection 3 weeks prior with subsequent rituximab treatment
20	Septic shock (colon perforation, Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumonia)	Crohn's disease, cachexia
21	Septic shock (pneumonia, Streptococcus pneumonia)	COPD
22	Septic shock (acute liver failure due to HSV)	Hysterectomy because of uterine myomas
23	Septic shock (MOF due to VZV)	Type 2 Diabetes

AML = acute myeloid leukemia, COPD = chronic obstructive pulmonary disease, GN = glomerulonephritis, MDS = myelodysplastic syndrome, MOF = multiple organ failure, OPSI = overwhelming post splenectomy infection, PBSCTx = peripheral blood stem cell transplantation, UIP = usual interstitial pneumonitis, VAHS = virus-associated hemohagocytotic syndrome, VZV = varizella zoster virus.

Table 2. Inflammation, organ dysfunction and outcome
Patient	Baseline PaO₂/F_iO₂(mmHg)	Baseline SOFA score	Baseline PCT (μg/l, ULN < 0.5)	Ventilatedor on ECMO during ICU stay	RRT during ICU stay	Organs failed during ICU stay	Discharge from ICU
1	140	5	13	Yes	No	4	No
2	381	12	54	No	Yes	3	Yes
3	89	15	18	Yes	Yes	5	No
4	86	17	25	Yes	Yes	5	Yes
5	117	11	0,1	Yes	Yes	5	No
6	293	11	34	Yes	Yes	6	Yes
7	240	16	400	Yes	Yes	5	No
8	58	15	94	Yes	Yes	5	Yes
9	56	20	12.8	Yes	Yes	5	Yes
10	220	4	0.6	Yes	Yes	1	Yes
11	107	13	1.8	Yes	Yes	4	No
12	102	18	47.8	Yes	Yes	4	No
13	200	10	2,5	Yes	No	1	No
14	108	7	0.1	Yes	Yes	2	No
15	351	9	107	Yes	Yes	5	Yes
16	67	11	182	Yes	Yes	4	No
17	192	13	30.6	Yes	Yes	5	Yes
18	335	11	37	Yes	Yes	4	Yes
19	83	16	337	Yes	Yes	5	No
20	50	17	3.6	Yes	No	5	No
21	80	16	84.7	Yes	Yes	5	No
22	283	16	13.7	Yes	Yes	5	No
23	93	19	9.6	Yes	Yes	6	No

ECMO = extracorporeal membrane oxygenation, FiO2 = fraction of inspired oxygen, ICU = intensive care unit, paO2 = arterial O2 partial pressure, PCT = procalcitonin, RRT = renal replacement therapy, SOFA = sepsis-related organ failure assessment, ULN = upper limit of normal.

Table 3. Details of plasma exchange therapy
Patient	BMI (kg/m²)	Time ICU admission to TPE (days)	No. of TPE procedures (day of application)	Plasma volume (ml)	Total Volume exchange per PV	Anti-coagulation	Membrane/Centrifuge
1	24.9	0	2 (1,2)	3.70	1.6	Heparin	M
2	22.4	1	4 (2,3,4,5)	3.57	4.1	Citrate	M
3	17.9	2	1 (3)	2.30	1.1	Citrate	M
4	21.6	0	1 (1)	3.17	0.8	Citrate	M
5	24.2	8	1 (9)	3.85	0.9	Heparin	M
6	15.1	7	3 (9,10,12)	2.07	1.5	Heparin	M
7	26.3	0	3 (1,3,6)	4.41	1.8	None	M
8	26.0	2	1 (3)	3.20	0.5	None	M
9	22.0	2	3 (3,4,5)	2.60	1.9	Citrate	M
10	22.0	1	3 (2,3,4)	3.30	3.3	Heparin	M
11	29.3	25	2 (25,26)	4.26	0.4	None	M
12	30.7	14	3 (14–16)	5.66	1.6	Heparin	M
13	22.9	11	2 (11,13)	3.77	1.3	Heparin	M
14	18.8	16	1 (16)	3.07	0.8	Heparin	M
15	21.4	0	1 (1)	2.60	1.4	None	M
16	20.0	2	2 (2,3)	2.15	2.8	Heparin	M
17	22.5	1	2 (2,3)	3.05	1.6	Citrate	M
18	24.2	0	3 (1,3,4)	3.87	2.6	Citrate	M
19	31.2	1	1 (2)	4.38	0.6	None	M
20	23.7	0	2 (1,2)	2.83	1.8	Heparin	M
21	24.9	1	1 (2)	3.47	0.9	Citrate	C
22	24.2	0	1 (1)	3.77	0.8	Citrate	M
23	24.2	1	1 (2)	4.20	0.9	Citrate	C