Effect of early goal directed therapy on tissue perfusion in patients with septic shock

doi:10.5847/wjem.j.issn.1920-8642.2013.02.006

Abstract

Abstract:

BACKGROUND: This study aimed to observe the effect of early goal directed therapy (EGDT) on tissue perfusion, microcirculation and tissue oxygenation in patients with septic shock.
METHODS: Patients with early septic shock (<24 hours) who had been admitted to the ICU of Zhongda Hospital Affiliated to Southeast University from September 2009 through May 2011 were enrolled (research time: 12 months), and they didn’t meet the criteria of EGDT. Patients who had one of the following were excluded: stroke, brain injury, other types of shock, severe heart failure, acute myocardial infarction, age below 18 years, pregnancy, end-stage disease, cardiac arrest, extensive burns, oral bleeding, difficulty in opening the mouth, and the onset of septic shock beyond 24 hours. Patients treated with the standard protocol of EGDT were included. Transcutaneous pressure of oxygen and carbon dioxide (PtcO₂, PtcCO₂) were monitored and hemodynamic measurements were obtained. Side-stream dark field (SDF) imaging device was applied to obtain sublingual microcirculation. Hemodynamics, tissue oxygen, and sublingual microcirculation were compared before and after EGDT. If the variable meets the normal distribution, Student’s t test was applied. Otherwise, Wilcoxon’s rank-sum test was used. Correlation between variables was analyzed with Pearson’s product-moment correlation coefficient method.
RESULTS: Twenty patients were involved, but one patient wasn’t analyzed because he didn’t meet the EGDT criteria. PtcO₂ and PtcCO₂ were monitored in 19 patients, of whom sublingual microcirculation was obtained. After EGDT, PtcO₂ increased from 62.7±24.0 mmHg to 78.0±30.9 mmHg (P<0.05) and tissue oxygenation index (PtcO₂/FiO₂) was 110.7±60.4 mmHg before EGDT and 141.6±78.2 mmHg after EGDT (P<0.05). The difference between PtcCO₂and PCO₂ decreased significantly after EGDT (P<0.05). The density of perfused small vessels (PPV) and microcirculatory flow index of small vessels (MFI) tended to increase, but there were no significant differences between them (P>0.05). PtcO₂, PtcO₂/FiO₂, and PtcCO₂ were not linearly related to central venous saturation, lactate, oxygen delivery, and oxygen consumption (P>0.05).
CONCLUSION: Peripheral perfusion was improved after EGDT in patients with septic shock, and it was not exactly reflected by the index of systemic perfusion.

Key words: Transcutaneous pressure of oxygen, Transcutaneous pressure of carbon dioxide, Microcirculation, Septic shock, EGDT, Tissue perfusion, Tissue oxygenation, Sidestream dark field imaging

Yuan-hua Lu, Ling Liu, Xiao-hua Qiu, Qin Yu, Yi Yang, Hai-bo Qiu. Effect of early goal directed therapy on tissue perfusion in patients with septic shock[J]. World Journal of Emergency Medicine, 2013, 4(2): 117-122.

Figures/Tables 8

Table 1

Table 2

Table 3

Table 4

Figure 1.

Table 5

Figure 2.

Figure 3.

References 17

1	Annane D, Aegerter P, Jars-Guincestre MC, Guidet B; CUB-Réa Network. Current epidemiology of septic shock: the CUB-Réa Network. Am J Respir Crit Care Med 2003; 168:165-172. doi: 10.1164/rccm.2201087 pmid: 12851245
2	Marty P, Roquilly A, Vallée F, Luzi A, Ferré F, Fourcade O, et al. Lactate clearance for death-prediction in severe sepsis or septic shock patients during the first 24 hours in Intensive Care Unit. An observational study. Ann Intensive Care 2013; 3:3. pmid: 23398782
3	Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377. doi: 10.1056/NEJMoa010307 pmid: 11794169
4	De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002; 166:98-104. pmid: 12091178
5	Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 2007; 49: 88-98, 98.e1-2.
6	Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 2004; 32:1825-1831. doi: 10.1097/01.ccm.0000138558.16257.3f pmid: 15343008
7	De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, et al. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 2006; 34:403-408. doi: 10.1097/01.ccm.0000198107.61493.5a pmid: 16424721
8	Tremper KK, Waxman K, Shoemaker WC. Effects of hypoxia and shock on transcutaneous PO₂ values in dogs. Crit Care Med 1979; 7:526-531.
9	Tremper KK, Shoemaker WC, Shippy CR, Nolan LS. Transcutaneous PCO₂ monitoring on adult patients in the ICU and the operating room. Crit Care Med 1981; 9:752-755. doi: 10.1097/00003246-198110000-00017 pmid: 6793314
10	Waxman K, Sadler R, Eisner ME, Applebaum R, Tremper KK, Mason GR. Transcutaneous oxygen monitoring of emergency department patients. Am J Surg 1983; 146:35-38. doi: 10.1016/0002-9610(83)90255-6 pmid: 6869677
11	Tatevossian RG, Wo CC, Velmahos GC, Demetriades D, Shoemaker WC. Transcutaneous oxygen and CO2 as early warning of tissue hypoxia and hemodynamic shock in critically ill emergency patients. Crit Care Med 2000; 28:2248-2253. pmid: 10921548
12	Society of Critical Care Medicine of Chinese Medical Association. Guidelines for hemodynamic monitoring and support of adult patients with severe sepsis and septic shock. Chin J Emerg Med 2007; 16:121-126.
13	Barbee RW, Reynolds PS, Ward KR. Assessing shock resuscitation strategies by oxygen debt repayment. Shock 2010; 33:113-122. doi: 10.1097/SHK.0b013e3181b8569d pmid: 20081495
14	Harrois A, Huet O, Duranteau J. Alterations of mitochondrial function in sepsis and critical illness. Curr Opin Anaesthesiol 2009; 22:143-149. doi: 10.1097/ACO.0b013e328328d1cc
15	Yu M, Morita SY, Daniel SR, Chapital A, Waxman K, Severino R. Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome. Shock 2006; 26:450-456. doi: 10.1097/01.shk.0000228798.18174.6a pmid: 17047514
16	Yu M, Chapital A, Ho HC, Wang J, Takanishi D Jr. A prospective randomized trial comparing oxygen delivery versus transcutaneous pressure of oxygen values as resuscitative goals. Shock 2007; 27:615-622. pmid: 17505300
17	Leone M, Blidi S, Antonini F, Meyssignac B, Bordon S, Garcin F, et al. Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock. Anesthesiology 2009; 111:366-371. doi: 10.1097/ALN.0b013e3181aae72d pmid: 19602965

Variables	mean±SD
Age (yr)	66.8±18.5
Sex (Male/Female)	14/5
APACHE II score	25.2±7.3
SOFA score	10.8±2.1
Temperature (°C)	38.0±1.2
HR (beats/minute)	115±27
MAP (mmHg)	72±12
PaCO₂ (mmHg)	36.4±11.9
Lactate (mmol/L)	2.3±1.5
White blood cell (×10⁹/L)	15.9±9.0
Creatinine (μmol/L)	118.7±52.0
Urea nitrogen (mmol/L)	12.7±8.5
Total bilirubin (μmol/L)	23.9±23.7
Albumin (g/L)	22.6±5.8
Vasoactive drugs ^a
Dopamine μg/kg per minute (n=12)	10.1±5.4
Norepinephrine μg/minute (n=9)	26.1±18.5
Dobutamine μg/kg per minute (n=4)	3.3±1.3
Source of infection ^a [n (%)]
Pneumonia	18 (94.7)
Abdominal infection	2 (10.5)
Other infection	4 (21.1)
Chronic complications ^a [n(%)]
Diabetes mellitus	4 (21.1)
Hypertension	10 (52.6)
Immunosuppression	6 (31.2)
Heart disease	8 (42.1)
Liver disease	2 (10.5)
Renal insufficiency	2 (10.5)

Variables	Before EGDT	After EGDT	t	P
HR (beats/minute)	115±27	108±22	2.644	0.017
MAP (mmHg)	72±12	84±9	5.764	0.000
CVP (mmHg)	7±2	11±2	8.027	0.000
CO (L/min)	8.49±2.97	8.94±3.37	0.806	0.436
CI (L/min?m^-2)	4.76±1.51	5.05±1.86	0.881	0.396
SV (mL)	71.8±31.5	78.5±36.8	1.278	0.226
SVI (mL/m²)	40.0±16.0	44.1±19.4	1.365	0.197
EVLWI (mL/kg)	15.5±5.5	15.5±6.0	0.023	0.982

Variables	Before EGDT	After EGDT	t /Z	P
pH	7.425±0.058	7.405±0.043	3.177	0.005
ScvO₂	0.766±0.081	0.807±0.062	2.907	0.009
DO₂ (mL?min^-1?m^-2)	618.0±252.5	677.5±250.9	1.419	0.181
VO₂ (mL?min^-1?m^-2)	117.8±53.1	113.5±36.8	0.411	0.688
O₂ext	0.202±0.071	0.176±0.050	1.622	0.131
Lac (mmol/L)	2.28±1.50	2.22±1.06	0.332	0.744
PaO₂(mmHg)	84.7 (69.2-119.2)	85.1 (81.3-102.6)	0.241	0.809
PcvO₂(mmHg)	48.4 (39.4-49.9)	49.4 (43.3-53.9)	2.335	0.020
PaO₂/FiO₂(mmHg) 153.8(105.8- 221.7)		163.5 (116.0-206.0)	0.684	0.494
Urine output (mL/kg per hour)	1.14±1.21	2.08±1.73	3.362	0.003

Variables	Before EGDT	After EGDT	t	P
TVD (mm/mm²)	20.16±5.05	19.48±4.85	0.290	0.791
PVD(mm/mm²)	16.14±4.81	17.88±4.19	0.578	0.604
PPV (%)	74.05±15.63	85.73±8.39	3.160	0.051
MFI	1.56±0.49	2.23±0.17	2.704	0.074
Heterogeneity index	0.29±0.05	0.26±0.14	0.479	0.665

Variables	Before EGDT	After EGDT	P
PtcO₂(mmHg)	62.7±24.0	78.0±30.9	0.016
PtcO₂/FiO₂(mmHg)	110.7±60.4	141.6±78.2	0.015
PtcO₂ shunt	0.309±0.355	0.185±0.300	0.024
PtcCO₂(mmHg)	37.0 (31.0-46.0)	36.0 (29.0-41.0)	0.009
PtcCO₂ index	1.05 (0.87-1.23)	1.02 (0.85-1.12)	0.025
PCO₂ gap(mmHg)	1.7 (-5.0-6.1)	0.6 (-5.50-3.50)	0.040