(Peripheral) Temperature and microcirculation · the microcirculation [1, 2, 3]. In addition, it...

(Peripheral) Temperature and microcirculation

Prof. Jan Bakker MD, PhD

Chair dept Intensive Care Adults

[email protected]

www.intensivecare.me

Thursday, March 22, 12

mailto:[email protected]

mailto:[email protected]

Intensive Care Med (2005) 31:1316–1326DOI 10.1007/s00134-005-2790-2 R EV I EW

Alexandre LimaJan Bakker Noninvasive monitoring of peripheral perfusion

Received: 21 February 2005Accepted: 4 August 2005Published online: 17 September 2005! Springer-Verlag 2005

This study was in part supported by mate-rials provided by Hutchinson Technologyand a grant from Philips USA. Both authorsreceived a grant US $12,000 from PhilipsUSA and $10,000 from Hutchinson Tech-nology.

A. Lima · J. Bakker ())Department of Intensive Care,Erasmus MC,University Medical Center Rotterdam,P.O. Box 2040, 3000 CA Rotterdam,The Netherlandse-mail: [email protected].: +31-10-4633629

Abstract Background: Early hemo-dynamic assessment of global pa-rameters in critically ill patients failsto provide adequate information ontissue perfusion. It requires invasivemonitoring and may represent a lateintervention initiated mainly in theintensive care unit. Noninvasivemonitoring of peripheral perfusioncan be a complementary approachthat allows very early applicationthroughout the hospital. In addition,as peripheral tissues are sensitive toalterations in perfusion, monitoringof the periphery could be an earlymarker of tissue hypoperfusion. Thisreview discusses noninvasive meth-ods for monitoring perfusion in pe-ripheral tissues based on clinicalsigns, body temperature gradient,optical monitoring, transcutaneousoximetry, and sublingual capnometry.Discussion: Clinical signs of poorperipheral perfusion consist of a cold,pale, clammy, and mottled skin, as-

sociated with an increase in capillaryrefill time. The temperature gradientsperipheral-to-ambient, central-to-pe-ripheral and forearm-to-fingertip skinare validated methods to estimatedynamic variations in skin bloodflow. Commonly used optical meth-ods for peripheral monitoring areperfusion index, near-infrared spec-troscopy, laser Doppler flowmetryand orthogonal polarization spec-troscopy. Continuous noninvasivetranscutaneous measurement of oxy-gen and carbon dioxide tensions canbe used to estimate cutaneous bloodflow. Sublingual capnometry is anoninvasive alternative for gastrictonometry.

Keywords Body temperaturegradient · Hemodynamic assessment ·Noninvasive monitoring · Peripheraltissue perfusion · Sublingualcapnometry · Transcutaneousoximetry

Introduction

An important goal of hemodynamic monitoring is theearly detection of inadequate tissue perfusion and oxy-genation to institute prompt therapy and guide resuscita-tion, avoiding organ damage. In clinical practice tissueoxygenation is frequently assessed by using conventionalglobal measurements such as blood pressure, oxygenderived variables, and blood lactate levels. However, theassessment of global hemodynamic parameters fails toreflect increased blood lactate levels, the imbalance be-tween oxygen demand and oxygen supply, or the status of

the microcirculation [1, 2, 3]. In addition, it often requiresinvasive monitoring techniques that usually limit earlyinitiation, typically after the patient has been admitted tothe intensive care unit (ICU).

To address these limitations there have been manyattempts to perform measurements of blood flow andoxygenation in peripheral tissues [4, 5]. In circulatoryfailure blood flow is diverted from the less importanttissues (skin, subcutaneous, muscle, gastrointestinal tract)to vital organs (heart, brain, kidneys). Thus monitoringperfusion in these less vital tissues could be an earlymarker of vital tissue hypoperfusion. Second, the assess-

•Clinical assessment• Temperature and temperature gradients

• Ttoe

• ΔT[Central-Toe], ΔT[Proximal-Distal]

•Optical monitoring• PFI, NIRS, OPS/SDF, LDF

• Transcutaneous PO2 and PCO2


Temperature and perfusionAnesthesiology 1988;68:836–842 ∞ 1988;69:357–364 ∞ 1990 73:541–545 ∞ 1995;83:1212-1219

r=0.98

Fore

arm

-Fin

ger T

grad

ient

(o C

)

Perf

usio

n In

dex

(u)


Correlates of thenar NIRS derived tissue O2 saturation after cardiac surgery Uilkema et al. Interact Cardiovasc Thorac Surg 2007;6(3):265-269

ARTICLE IN PRESS

267R.J. Uilkema, A.B.J. Groeneveld / Interactive CardioVascular and Thoracic Surgery 6 (2007) 265–269

Table 1Patient characteristics (ns23)

Age, years 70 (46–84)Maleyfemale 14y9Type of surgery

CABG 9Mitral valve reconstruction 3CABG and aortic valve replacement 4Aortic valve replacement 5CABG and mitral valve reconstruction 1CABG and mitral valve replacement 1

CPB time, min 111 (50–210)Aortic clamping time, min 79 (39–146)Mechanical ventilation, duration, h 10 (5–48)

Median and range or number of patients, where appropriate; CABG, coro-nary artery bypass grafting; CPB, cardiopulmonary bypass.

Fig. 1. Changes in NIRS-derived tissue O saturation (S O ) versus changes in2 t 2

body-finger temperature difference as a function of time in the patients:r sy0.48, P-0.001.s

Table 2Global, peripheral and blood variables

Admission ts2 h ts4 h ts18–22 h Pns23 ns23 ns22 ns20

Global variablesBody temperature, 8C 35.7 (34.7–36.8) 36.0 (35.1–36.9) 36.5 (35.8–37.2) 36.8 (35.9–47.4) -0.001MABP, mmHg 72 (52–84) 69 (51–88) 75 (55–102) 87 (60–111) 0.001CVP, mmHg 6 (3–16) 6 (3–14) 7 (3–13) 10 (5–15) 0.02CI, lØmin Ømy y1 2 2.9 (1.6–4.4) 2.6 (1.5–3.3) 2.6 (1.3–3.5) 2.4 (1.2–3.8) nsDopamine, numberydose mgØminy1 9y0 (0–36) 9y0 (0–64) 7y0 (0–96) 2y0 (0–40) nsNitroglycerine, numberydose mgØminy1 13y0.25 (0–0.5) 10y0 (0–0.2) 9y0 (0–0.2) 1y0.25 0.001

Peripheral variablesDiuresis, mlØhy1 205 (50–500) 125 (50–390) 90 (0–500) 58 (21–150) -0.001Finger temperature, 8C 31.5 (29.4–34.4) 32.2 (29.8–35.1) 33.2 (31.3–36.0) 32.5 (28.8–36.2) 0.001Body-finger temperature,8C 4.1 (1.0–7.4) 3.5 (0.6–6.2) 3.3 (0.3–5.8) 4.6 (0.7–6.5) 0.008Pulse oxymetry S O , %p 2 99 (96–100) 98 (96–100) 98 (96–100) 98 (91–100) 0.007NIRS S O , %t 2 93 (75–98) 91 (76–98) 91 (78–98) 85 (52–97) 0.001NIRS %HT 0.18 (0.14–0.26) 0.18 (0.12–0.26) 0.18 (0.12–0.26) 0.16 (0.09–0.21) -0.001

BloodP O , mmHga 2 118 (69–209) 142 (68–198) 138 (81–203) 101 (63–183) 0.03S O , %a 2 98 (96–99) 98 (96–99) 98 (90–99) 98 (94–99) nsS O , %mv 2 78 (67–91) 75 (61–87) 73 (47–83) 73 (40–81) 0.01Hb, mmolØly1 6.1 (4.8–7.3) 6.1 (4.0–7.5) 6.4 (4.4–7.3) 7.1 (5.1–8.6) -0.001Hct 0.28 (0.23–0.35) 0.29 (0.21–0.36) 0.29 (0.21–0.35) 0.34 (0.24–0.41) -0.001Lactate, mmolØly1 1.4 (0.8–4.3) 1.4 (0.1–3.8) 1.7 (0.7–4.0) 1.2 (0.7–3.4) ns

Median and range. MABP, mean arterial blood pressure; CVP, central venous pressure; CI, cardiac index; NIRS, near-infrared spectroscopy; S O , tissue Ot 2 2

saturation; %HT, tissue haemoglobin content; PO , partial O pressure in arterial (a) blood; SO , O saturation in arterial (a) or mixed venous (mv) blood; Hb,2 2 2 2

haemoglobin; Hct, haematocrit. Exact P if F0.05, nssnon-significant.

3. Results

A total of 23 patients were included in the study, andcharacteristics are given in Table 1, showing that removalof catheters or discharge from the ICU precluded measure-ments after ICU admission in a few patients. All patientssurvived to hospital discharge and only three patientsstayed for more than one day in the IC, before dischargeto specialised cardiac surgery wards.

Table 2 describes the postoperative course of global,peripheral and NIRS variables. It is shown that NIRS-derived%HT and S O declined as a function of time, concomitantlyt 2

with a fall in diuresis and rise in body-finger temperaturegradient despite a rise in body and finger temperature.The CI did not change but MABP rose, concomitantly withtapering doses of nitroglycerine and rises in CVP. S O ,mv 2

P O and S O fell while S O was unchanged. Blood HbyHcta 2 p 2 a 2

rose.

3.1. Correlations

For pooled data, the S O , NIRS-derived S O and CImv 2 t 2

interrelated (minimum r s0.33, Ps0.002), but not fors

changes in these variables in the course of time, exceptfor a direct relation between changes in CI and S Omv 2

(Ps0.003). For pooled data, the NIRS-derived S O relatedt 2

to urinary production (r s0.32, Ps0.003) and tended tos

relate to body-finger temperature differences (r sy0.21,s

Ps0.057), while changes in time in body-finger tempera-ture difference best correlated to changes in NIRS-derivedS O : r sy0.48, P-0.001 (Fig. 1) and not to changes int 2 s

%HT. Otherwise, S O highy correlated to NIRS-derived %HT,t 2

for pooled data and changes in time (r s0.77, P-0.001).s

23 patients70 yr (46-84)Duration MV 10h (5-48)CABG: 9CABG+valve: 6AVR: 5MVR: 3

rs 0.48, P<0.001


Vascular Occlusion Test 1

3 min

30 mm Hgabove SAP


Peripheral vasoconstriction influences thenar oxygen saturation as measured by NIRSLima et al. Intensive Care Med 2012 (in press)

• 8 healthy volunteers (26±6 yr)

• use of cooling blanket

• cooling of the periphery without change in core temperature (tympanic temperature)

• water temperature 32oC

• measurements: baseline, 30’ after start cooling, 30’ after suspension of cooling (rewarmed)

• StO2 measured with 15 mm probe on thenar muscle

• CO measured by NICOM (Cheetah)

• Skin vasoconstriction: 50% decrease in Tskin-diff or PI



Baseline Cold 30’

Rewarmed30’

HR (b/min)

MAP (mmHg)

SV (ml)

CO (L/min)

Core Temp (oC)

76 [70-83] 67 [58-73] 70 [67-74]

93 [88-101] 100 [92-107] 95 [87-100]

110 [76-125] 139 [132-147] 114 [106-164]

8,6 [8,0-9,4] 10,1 [8,9-12,2] 7,9 [7,3-10,1]

36,8 [36,6-36,9] 36,6 [36,4-36,9] 36,6 [36,4-36,9]

median [IQR]



Baseline Cold 30’

Rewarmed30’

StO2 (%)

RincStO2 (%/sec)

Tskin-diff (oC)

CRT (sec)

PI (%)

82 [80-87] 72 [70-77] * 80 [79-85]

3,0 [2,8-3,3] 1,7 [1,1-2,0] * 3,2 [3,0-4,2]

1,0 [-1,6-1,8] 3,1 [1,8-4,3] * 1,2 [-0,3-2,7]

2,5 [2,0-3,0] 8,5 [7,2-11,0] * 4,0 [3,0-5,7]

10,0 [9,1-11,7] 2,5 [2,0-3,8] * 9,1 [8,2-11,7]

median [IQR]




Relation of NIRS with changes in peripheral circulation in critically ill patientsLima et al. Crit Care Med 2011;39:1649-1654

‣73 critically ill patients

‣Age: 57 (17-90)

‣ SOFA: 6 (1-15)

‣APACHE II: 23 (6-35)

‣ Septic shock n=33

‣ Shock without sepsis: n= 25

‣No shock or sepsis: n=15


mixed linear model over 3 daysUpslope (%/s)

estimate (95% CI)

HR b/min

MAP (mmHg)

Abnormal Peripheral Circulation

-0.001 (-0.09;0.09)

-0.02 (-0.13;0.075)

-1.1 (-0.8;-1.4)**

Relation of NIRS with changes in peripheral circulation in critically ill patientsLima et al. Crit Care Med 2011;39:1649-1654


Skin temperature and systemic circulation

Cool

2.9 ± 1.2

7.32 ± 0.2

60 ± 4

4.7 ± 1.5

Cardiac Index

Arterial pH

SvO2

Lactate

Warm

4.3 ± 1.2 *

7.39 ± 0.07 *

68 ± 8 *

2.2 ± 1.6 *

• Cool vs. warm skin§ Similar: Heart rate, blood pressure, PAOP, Hemoglobin, FiO2, PaO2, PaCO2

Kaplan et al. J Trauma 2001;50:620-628


statistically significant between patientswith and without unfavorable evolution(data not shown). The proportion of pa-tients with hyperlactatemia was signifi-cantly higher in patients with abnormalperipheral perfusion (Table 5). Logisticregression analysis showed that the oddsof hyperlactatemia in a patient with ab-normal peripheral perfusion are 4.6 (95%confidence interval 1.4–15; p ! 0.05)times higher than in a patient with nor-mal peripheral perfusion.

DISCUSSION

This prospective observational studyshows that the subjective assessment ofperipheral perfusion could discriminatepatients with a more severe organ dys-function, as expressed by high SOFA

score and lactate levels in patients withabnormal peripheral perfusion. One mayargue that high SOFA score in the abnor-mal peripheral perfusion group may berelated to the level of mean arterial pres-sure or to the use of vasopressor support.However, our patients were all resusci-tated and stabilized at the moment thatdata were collected, and global hemody-namic variables or dose of vasopressorwas similar between patients with normaland abnormal peripheral perfusion. Thisfinding suggests that abnormal periph-eral perfusion is not related to hypoten-sion or vasoconstriction from a pharma-cologic intervention. This lack ofassociation between abnormal peripheralperfusion and global hemodynamic vari-ables is not unexpected, because somestudies have reported a poor correlationbetween clinical examination of periph-

eral perfusion and heart rate, blood pres-sure, or cardiac output (3, 10, 17). Inaddition, recent observations suggestthat microcirculatory alterations in cir-culatory shock are independent of sys-temic variables (18, 19) and that systemicvariables may not be sensitive enough toreflect changes in peripheral blood flowin critically ill patients (20).

Delta-SOFA score has been suggestedto monitor the evolution of organ failure(16). In our study, we investigatedwhether the condition of peripheral per-fusion in resuscitated patients could pre-dict an increase in severity of organ dys-function. Our results show that patientswho persist with abnormal peripheralperfusion after initial resuscitation have asignificantly higher probability of unfa-vorable evolution, as indicated by an in-crease in the "-SOFA score. Thus, moni-toring peripheral perfusion could identifythese patients who do not improve de-spite initial resuscitation and stabiliza-tion. Similarly, the logistic regressionanalysis showed that patients who havean abnormal peripheral perfusion follow-ing resuscitation are more likely to re-main hyperlactatemic. The interpretationof hyperlactatemia in critically ill patientsis complex, and factors other than hypo-perfusion may be involved (21). Never-theless, our findings are in agreementwith those of Kaplan et al (6) showingthat patients with cold extremities areassociated with higher blood lactate lev-els. The correlation between abnormalperipheral perfusion and high blood lac-tate levels in our patients is not surpris-ing as hyperlactatemia in most casestakes place in the presence of organ dys-function (22–24). This prospective studydoes not show a causal relation betweenpoor peripheral perfusion and organ dys-function or tissue hypoperfusion, butsome reports indicate this relation (1,25–27). Studies on measurements ofblood flow and oxygenation in peripheraltissues suggest that compensatory vaso-constriction results in maldistribution ofmicrocirculatory flow, which has been as-sociated with organ dysfunction and mul-tiple organ failure (1, 25–27).

In a recent consensus conference onhemodynamic monitoring in shock, itwas recognized that the definition ofshock requires evidence of circulatoryand cellular dysfunction, manifested bymarkers of hypoperfusion such as ele-vated blood lactate levels, regardless ofthe presence of hypotension (20). Be-cause data were collected in the post-

Table 2. Objective parameters of peripheral circulation according to the subjective evaluation ofperipheral perfusion

Objective Parameters

Subjective Evaluation

pNormal (n # 27) Abnormal (n # 23)

Tskin-diff (°C) $0.2 % 2.8 4.6 % 2.8 !0.01Tc-toe (°C) 6.5 % 3.4 10 % 4.1 !0.01PFI 2.3 % 1.6 0.7 % 0.8 !0.01

Tskin-diff, forearm-to-fingertip skin-temperature gradient; Tc-toe, central-to-toe temperature differ-ence; PFI, peripheral flow index.

Table 3. Global hemodynamics variables in abnormal and normal peripheral perfusion

Peripheral Perfusion

pNormal (n # 27) Abnormal (n # 23)

HR (bpm) 90 % 22 94 % 20 0.53MAP (mm Hg) 80 % 14 81 % 18 0.87CVP (mm Hg) 14 % 6 13 % 7 0.84Urine output (mL/hr) 111 % 83 72 % 30 0.14

HR, heart rate; MAP, mean arterial blood pressure; CVP, central venous pressure.

Table 4. Proportion of patients with unfavorableevolution ("-SOFA &0) and favorable evolution("-SOFA score !0) stratified by normal and ab-normal peripheral perfusiona


Normal(n # 27)

Abnormal(n # 23)

"-SOFA !0 (N # 33),percent of patients

70 30

"-SOFA &0 (N # 17),percent of patients

23 77

SOFA, Sequential Organ Failure Assessmentscore.

ap ! 0.05, by chi-square test.

Table 5. Proportion of hyperlactatemia and nor-mal blood lactate levels between patients withabnormal and normal peripheral perfusiona


Normal(n # 27)

Abnormal(n # 23)

Normal lactate levels(N # 29), percentof patients

69 31

Hyperlactatemia(N # 21), percentof patients

33 67

ap ! 0.05, by chi-square test.

936 Crit Care Med 2009 Vol. 37, No. 3

The prognostic value of the subjective assessment of peripheralperfusion in critically ill patients

Alexandre Lima, MD; Tim C. Jansen, MD; Jasper van Bommel, MD, PhD; Can Ince, PhD;Jan Bakker, MD, PhD

Clinical signs of poor periph-eral perfusion have beenshown to be an early markerof inadequate tissue perfusion

in acute circulatory shock (1–3). The ra-tionale of monitoring peripheral perfu-sion is based on the concept that duringhypotension the sympathetic neurohu-moral response predominates on periph-

eral tissues resulting in a decreased skinperfusion and temperature (4, 5). Thus,monitoring of peripheral perfusion canassess the effect of the neurohumoralcompensatory mechanism induced bylow flow shock states in an acute stage ofthe disease.

Studies have showed that the subjec-tive assessment of peripheral perfusion,in particular, the physical examination bytouching the skin or measuring capillaryrefill time, can identify patients at highrisk of complications from acute circula-tory shock (6–9). Hasdai et al (7) showedthe importance of the physical examina-tion of peripheral perfusion in determin-ing the prognosis of patients with cardio-genic shock. In their study, the presenceof a cold and clammy skin was an inde-pendent predictor of 30-day mortality. Al-

though septic shock is associated withperipheral vasodilation, cool extremitiesmay be present in the early stage of sep-sis. In another recent study, Thompson etal (8) studied the time course of the clin-ical features of meningococcal disease inchildren and adolescents before the ad-mission to the hospital, and they identi-fied cold hands and feet together withabnormal skin color as the main impor-tant clinical signs within the first 12hours of the onset of illness. From thesestudies, it is clear that subjective assess-ment of peripheral perfusion is a valuableadjunct in hemodynamic monitoringduring circulatory shock, and should bethe first approach to assess critically illpatients.

However, most studies on clinical as-sessment of peripheral perfusion have fo-

From the Department of Intensive Care, ErasmusMC University Hospital Rotterdam, Rotterdam, TheNetherlands.

Supported by department funds.The authors have not disclosed any potential con-

flicts of interest.For information regarding this article, E-mail:

[email protected] © 2009 by the Society of Critical Care

Medicine and Lippincott Williams & Wilkins

DOI: 10.1097/CCM.0b013e31819869db

Objective: The physical examination of peripheral perfusionbased on touching the skin or measuring capillary refill time hasbeen related to the prognosis of patients with circulatory shock.It is unclear, however, whether monitoring peripheral perfusionafter initial resuscitation still provides information on morbidity incritically ill patients. Therefore, we investigated whether subjec-tive assessment of peripheral perfusion could help identify criti-cally ill patients with a more severe organ or metabolic dysfunc-tion using the Sequential Organ Failure Assessment (SOFA) scoreand lactate levels.

Design: Prospective observational study.Setting: Multidisciplinary intensive care unit in a university

hospital.Patients: Fifty consecutive adult patients admitted to the in-

tensive care unit.Interventions: None.Measurements and Main Results: Patients were considered to

have abnormal peripheral perfusion if the examined extremity hadan increase in capillary refill time (>4.5 seconds) or it was coolto the examiner hands. To address reliability of subjective inspec-tion and palpation of peripheral perfusion, we also measuredforearm-to-fingertip skin-temperature gradient (Tskin-diff), central-to-toe temperature difference (Tc-toe), and peripheral flow index.The measurements were taken within 24 hours of admission tothe intensive care after hemodynamic stability was obtained(mean arterial pressure >65 mm Hg). Changes in SOFA score

during the first 48 hours were analyzed (!-SOFA). Individual SOFAscore was significantly higher in patients with abnormal periph-eral perfusion than in those with normal peripheral perfusion (9 "3 vs. 7 " 2, p < 0.05). Tskin-diff, Tc-toe, and peripheral flow indexwere congruent with the subjective assessment of peripheralperfusion. The proportion of patients with !-SOFA score >0 wassignificantly higher in patients with abnormal peripheral perfu-sion (77% vs. 23%, p < 0.05). The logistic regression analysisshowed that the odds of unfavorable evolution are 7.4 (95%confidence interval 2–19; p < 0.05) times higher for a patient withabnormal peripheral perfusion. The proportion of hyperlactatemiawas significantly different between patients with abnormal andnormal peripheral perfusion (67% vs. 33%, p < 0.05). The odds ofhyperlactatemia by logistic regression analysis are 4.6 (95%confidence interval 1.4–15; p < 0.05) times higher for a patientwith abnormal peripheral perfusion.

Conclusions: Subjective assessment of peripheral perfusionwith physical examination following initial hemodynamic resus-citation in the first 24 hours of admission could identify hemo-dynamically stable patients with a more severe organ dysfunctionand higher lactate levels. Patients with abnormal peripheral per-fusion had significantly higher odds of worsening organ failurethan did patients with normal peripheral perfusion followinginitial resuscitation. (Crit Care Med 2009; 37:934–938)

KEY WORDS: physical examination; capillary refill; skin temper-ature; body temperature; critically ill; multiple organ failure

934 Crit Care Med 2009 Vol. 37, No. 3

Crit Care Med 2009; 37:934–938

cused on specific populations of patientsor have been performed during resusci-tation in an acute stage of the disease (3,8–10). It is unclear whether monitoringperipheral perfusion with physical exam-ination in a general population of theintensive care unit (ICU) after initial re-suscitation still provides informationabout organ derangements and whetherit predicts outcome in terms of organdysfunction.

In view of these observations, we car-ried out a prospective study to evaluatewhether subjective assessment of periph-eral perfusion in the postresuscitationphase of patients admitted to a generalICU could predict organ dysfunction. Inparticular, we wished to investigate ifclinical monitoring of peripheral perfu-sion could help identify patients with amore severe organ dysfunction or meta-bolic dysfunction, as expressed by highSequential Organ Failure Assessment(SOFA) score and lactate levels.

MATERIALS AND METHODS

Study Design and Patients. This prospec-tive observational study was conducted in theintensive care of a university hospital, admit-ting all patients except those following cardiacsurgery. We enrolled consecutive critically illpatients who had undergone initial resuscita-tion and stabilization within 24 hours of ICUadmission. Patients were excluded if they hadsevere peripheral vascular disease (with a his-tory of vascular surgery). The InstitutionalReview Board approved the study. Each pa-tient or relative provided written informedconsent.

Measurements. The assessment of periph-eral perfusion was based on the subjectiveevaluation of the examiner, and patients wereconsidered to have abnormal peripheral per-fusion if the examined extremity had an in-crease in capillary refill time or it was cool tothe examiner’s hands. Capillary refill time wasmeasured by applying firm pressure to thedistal phalanx of the index finger for 15 sec-onds. A chronometer recorded the time forreturn of the normal color and 4.5 secondswas defined as the upper limit of normality(11). To address the reliability of the subjectiveassessment of peripheral perfusion by the ex-aminer, we also measured forearm-to-finger-tip skin-temperature gradient (Tskin-diff), cen-tral-to-toe temperature difference (Tc-toe), andperipheral flow index (PFI) simultaneouslywith clinical observation. The Tskin-diff was ob-tained from two skin probes (Hewlett Packard21078A, Palo Alto, CA) attached to the indexfinger and on the radial side of the forearm,mid-way between the elbow and the wrist. TheTc-toe was calculated from central tempera-ture, with an infrared tympanic thermometer(First Temp Genius Thermometer—3000A;

Kendall Healthcare, Mansfield, MA), and greattoe temperature measured on the ventral facewith a skin probe (Hewlett Packard 21078A).The temperature gradients Tskin-diff and Tc-toecan better reflect cutaneous blood flow thanthe skin temperature itself. Considering a con-stant environment condition, Tskin-diff andTc-toe increases during vasoconstriction (12,13). PFI provides a noninvasive method toevaluate and to reflect changes in peripheralperfusion (14, 15). PFI is derived from thepulse oximetry signal and it was measuredusing the Nellcor-OxiMax pulse oximetry(Boulder, CO) and the Hewlett Packard mon-itor (Viridia/56S). To confirm the subjectiveassessment of abnormal peripheral perfusioncondition, this study used the following defi-nition of vasoconstriction: Tskin-diff !0°C (12),Tc-toe !7°C (13), and PFI "1.4 (14). Althoughthe ambient temperature at each patient’sbedside was not directly measured, the ICUhas one-person closed rooms and the ambienttemperature in each patient room was individ-ually and actively controlled at 22°C. Thereaf-ter, routine global hemodynamic variablessuch as heart rate, mean arterial pressure,central venous pressure, and urine outputwere obtained.

Basic demographic characteristics and allthe variables of SOFA score were collected foreach patient. The investigator registered themeasurements within 24 hours of admissionto the intensive care after hemodynamic sta-bility was obtained (mean arterial pressure!65 mm Hg and no change in vasopressorinfusion rate for 2 hours). Changes in SOFAscore during the first 48 hours (#-SOFA) werealso analyzed and was calculated as the differ-ence between the 48-hour SOFA score and theadmission score (16). Arterial blood sampleswere withdrawn for the determination ofblood gases and lactate levels. Hyperlactatemiawas defined as a blood lactate level !2mmol/L. We were interested in evaluatingwhether subjective assessment of peripheralperfusion could help identify patients with un-favorable evolution defined as #-SOFA score!0 and hyperlactatemia.

Statistics. The results are presented asmean $ SD, unless otherwise specified. Differ-ences between group means were tested byStudent’s t tests, and for variables that werenot normally distributed, by Mann-Whitney Utest. The chi-square test was used to comparefrequencies. To estimate the association be-tween abnormal peripheral perfusion andboth #-SOFA score and hyperlactatemia, lo-gistic regression analysis was performed. pvalues !0.05 were considered statisticallysignificant.

RESULTS

Of 50 patients included in the study,39 had circulatory shock at admission toICU, of whom 21 had septic shock and 18had no septic shock. Table 1 summarizes

the clinical data of the patients. Duringthe first 24 hours of ICU admission, 23patients (46%) had abnormal peripheralperfusion following resuscitation and sta-bilization. Individual SOFA score was sig-nificantly higher in patients with abnor-mal peripheral perfusion than in thosewith normal peripheral perfusion (9 $ 3vs. 7 $ 2, p " 0.05). Tskin-diff, Tc-toe, andPFI measurements were congruent withthe subjective assessment of peripheralperfusion (Table 2). Hemodynamic vari-ables were similar in patients with abnor-mal and normal peripheral perfusion (Ta-ble 3). In patients who receivedvasopressor therapy (n % 33), the dose ofvasopressor did not differ between nor-mal (n % 17) and abnormal (n % 16)peripheral perfusion condition (0.19 $0.11 vs. 0.17 $ 0.10; p % 0.80).

The proportion of patients with unfa-vorable evolution was significantly higherin patients with abnormal peripheral per-fusion (Table 4). Logistic regression anal-ysis showed that the odds of unfavorableevolution are 7.4 (95% confidence inter-val 2–19; p " 0.05) times higher for apatient with abnormal peripheral perfu-sion than for a patient with normal pe-ripheral perfusion. Differences in globalhemodynamic variables, such as heartrate, mean arterial pressure, central ve-nous pressure, and urine output were not

Table 1. Demographic data of the patients

Number of patients 50Age (yrs) 51 (17–80)Male/female 39/11Sequential Organ Failure

Assessment score admission8 (2–15)

Acute Physiology and ChronicHealth Evaluation II

23 (13–35)

Admission categoryPneumonia 9Trauma 8Abdominal sepsis 7Postoperative 5Chronic obstructive

pulmonary disease3

Cardiogenic shock 2Hepatic encephalopathy 2Hypovolemic/hemorrhagic

shock2

Mediastinitis 2Meningitis 2Pancreatitis 2Postcardiac arrest 2Cerebrovascular accident 1Lung cancer 1Systemic lupus erythematosus 1Urosepsis 1Survivor/nonsurvivor 35/15

Values are given as mean (range) whereap-propriate.

935Crit Care Med 2009 Vol. 37, No. 3

Patients with abnormal peripheral perfusion

• were more likely to have increased lactate • had significantly less decreases in lactate levels• had OR 7.4 of increasing organ failure


Peripheral perfusioncardiogenic shock

Odd’s ratio for day-30 mortality

‣Oliguria 3.4 (2.8 - 4.2)

‣Altered sensorium 2.1 (1.7 - 2.5)

‣Cold, clammy skin 1.8 (1.5 - 2.3)

Gusto I trial: 41.021 patients Am Heart J 1999;138:21-31


Available online http://ccforum.com/content/13/S5/S13

Page 1 of 7(page number not for citation purposes)

AbstractIntroduction: The prognostic value of continuous monitoring oftissue oxygen saturation (StO2) during early goal-directed therapyof critically ill patients has not been investigated. We conductedthis prospective study to test the hypothesis that the persistence oflow StO2 levels following intensive care admission is related toadverse outcome.Methods: We followed 22 critically ill patients admitted withincreased lactate levels (>3 mmol/l). Near-infrared spectroscopy(NIRS) was used to measure the thenar eminence StO2 and the rateof StO2 increase (RincStO2) after a vascular occlusion test. NIRSdynamic measurements were recorded at intensive care admissionand each 2-hour interval during 8 hours of resuscitation. All repeatedStO2 measurements were further compared with Sequential OrganFailure Assessment (SOFA), Acute Physiology and Chronic HealthEvaluation (APACHE) II and hemodynamic physiological variables:heart rate (HR), mean arterial pressure (MAP), central venous oxygensaturation (ScvO2) and parameters of peripheral circulation (physicalexamination and peripheral flow index (PFI)).Results: Twelve patients were admitted with low StO2 levels (StO2<70%). The mean scores for SOFA and APACHE II scores weresignificantly higher in patients who persisted with low StO2 levels(n = 10) than in those who exhibited normal StO2 levels (n = 12) at8 hours after the resuscitation period (P <0.05; median(interquartile range): SOFA, 8 (7 to 11) vs. 5 (3 to 8); APACHE II,32 (24 to 33) vs. 19 (15 to 25)). There was no significantrelationship between StO2 and mean global hemodynamic variables(HR, P = 0.26; MAP, P = 0.51; ScvO2, P = 0.11). However, therewas a strong association between StO2 with clinical abnormalitiesof peripheral perfusion (P = 0.004), PFI (P = 0.005) and RincStO2(P = 0.002). The persistence of low StO2 values was associatedwith a low percentage of lactate decrease (P <0.05; median(interquartile range): 33% (12 to 43%) vs. 43% (30 to 54%)).Conclusions: We found that patients who consistently exhibitedlow StO2 levels following an initial resuscitation had significantlyworse organ failure than did patients with normal StO2 values, andfound that StO2 changes had no relationship with global hemo-dynamic variables.

IntroductionA more complete evaluation of tissue perfusion can beachieved by adding non-invasive assessment of peripheralperfusion to global parameters [1]. Non-invasive monitoring ofperipheral perfusion is an alternative approach that allowsvery early application throughout the hospital, including theemergency department, operating room, and hospital wards.The rationale of monitoring peripheral perfusion is based onthe concept that peripheral tissues are the first to reflecthypoperfusion in shock and the last to reperfuse duringresuscitation [1,2]. Poor peripheral perfusion may thereforebe considered an early predictor of tissue hypoperfusion anda warning signal of ongoing shock.

In the clinical practice, non-invasive monitoring of peripheralperfusion can be performed easily using current newtechnologies, such as near-infrared spectroscopy (NIRS) [3].NIRS technology has been used as a tool to monitor tissueoxygen saturation (StO2) in acutely ill patients [4]. In addition,the analysis of changes in StO2 during a vascular occlusiontest, such as a brief episode of forearm ischemia, has beenused as a marker of integrity of the microvasculature – inparticular, the StO2 recovery after the vascular occlusion test[5-7]. These reports, however, have studied the correlation ofintermittent StO2 measurements and outcome where thereare only limited data describing whether continuous monitor-ing of StO2 during the early resuscitation phase is related tomorbidity or to mortality.

We therefore conducted the present prospective obser-vational study to investigate the association betweencontinuous StO2 measurements during early resuscitation ofhigh-risk patients and subsequent adverse outcomes. Theprimary study objective was to investigate whether persis-

Research Low tissue oxygen saturation at the end of early goal-directedtherapy is associated with worse outcome in critically ill patientsAlexandre Lima, Jasper van Bommel, Tim C Jansen, Can Ince and Jan Bakker

Department of Intensive Care, Room HS3.20, Erasmus MC University Medical Centre Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands

Corresponding author: Prof. Jan Bakker, [email protected]

Published: 30 November 2009 Critical Care 2009, 13(Suppl 5):S13 (doi:10.1186/cc8011)This article is online at http://ccforum.com/content/13/S5/S13© 2009 BioMed Central Ltd

APACHE = Acute Physiology and Chronic Health Evaluation; HR = heart rate; ICU = intensive care unit; MAP = mean arterial pressure; NIRS =near-infrared spectroscopy; PFI = peripheral flow index; RincStO2 = rate of tissue oxygen saturation increase; SOFA = Sequential Organ FailureAssessment; StO2 = tissue oxygen saturation; ScvO2 = central venous oxygen saturation.



AbstractIntroduction: The prognostic value of continuous monitoring oftissue oxygen saturation (StO2) during early goal-directed therapyof critically ill patients has not been investigated. We conductedthis prospective study to test the hypothesis that the persistence oflow StO2 levels following intensive care admission is related toadverse outcome.Methods: We followed 22 critically ill patients admitted withincreased lactate levels (>3 mmol/l). Near-infrared spectroscopy(NIRS) was used to measure the thenar eminence StO2 and the rateof StO2 increase (RincStO2) after a vascular occlusion test. NIRSdynamic measurements were recorded at intensive care admissionand each 2-hour interval during 8 hours of resuscitation. All repeatedStO2 measurements were further compared with Sequential OrganFailure Assessment (SOFA), Acute Physiology and Chronic HealthEvaluation (APACHE) II and hemodynamic physiological variables:heart rate (HR), mean arterial pressure (MAP), central venous oxygensaturation (ScvO2) and parameters of peripheral circulation (physicalexamination and peripheral flow index (PFI)).Results: Twelve patients were admitted with low StO2 levels (StO2<70%). The mean scores for SOFA and APACHE II scores weresignificantly higher in patients who persisted with low StO2 levels(n = 10) than in those who exhibited normal StO2 levels (n = 12) at8 hours after the resuscitation period (P <0.05; median(interquartile range): SOFA, 8 (7 to 11) vs. 5 (3 to 8); APACHE II,32 (24 to 33) vs. 19 (15 to 25)). There was no significantrelationship between StO2 and mean global hemodynamic variables(HR, P = 0.26; MAP, P = 0.51; ScvO2, P = 0.11). However, therewas a strong association between StO2 with clinical abnormalitiesof peripheral perfusion (P = 0.004), PFI (P = 0.005) and RincStO2(P = 0.002). The persistence of low StO2 values was associatedwith a low percentage of lactate decrease (P <0.05; median(interquartile range): 33% (12 to 43%) vs. 43% (30 to 54%)).Conclusions: We found that patients who consistently exhibitedlow StO2 levels following an initial resuscitation had significantlyworse organ failure than did patients with normal StO2 values, andfound that StO2 changes had no relationship with global hemo-dynamic variables.

IntroductionA more complete evaluation of tissue perfusion can beachieved by adding non-invasive assessment of peripheralperfusion to global parameters [1]. Non-invasive monitoring ofperipheral perfusion is an alternative approach that allowsvery early application throughout the hospital, including theemergency department, operating room, and hospital wards.The rationale of monitoring peripheral perfusion is based onthe concept that peripheral tissues are the first to reflecthypoperfusion in shock and the last to reperfuse duringresuscitation [1,2]. Poor peripheral perfusion may thereforebe considered an early predictor of tissue hypoperfusion anda warning signal of ongoing shock.

In the clinical practice, non-invasive monitoring of peripheralperfusion can be performed easily using current newtechnologies, such as near-infrared spectroscopy (NIRS) [3].NIRS technology has been used as a tool to monitor tissueoxygen saturation (StO2) in acutely ill patients [4]. In addition,the analysis of changes in StO2 during a vascular occlusiontest, such as a brief episode of forearm ischemia, has beenused as a marker of integrity of the microvasculature – inparticular, the StO2 recovery after the vascular occlusion test[5-7]. These reports, however, have studied the correlation ofintermittent StO2 measurements and outcome where thereare only limited data describing whether continuous monitor-ing of StO2 during the early resuscitation phase is related tomorbidity or to mortality.

We therefore conducted the present prospective obser-vational study to investigate the association betweencontinuous StO2 measurements during early resuscitation ofhigh-risk patients and subsequent adverse outcomes. Theprimary study objective was to investigate whether persis-

Research Low tissue oxygen saturation at the end of early goal-directedtherapy is associated with worse outcome in critically ill patientsAlexandre Lima, Jasper van Bommel, Tim C Jansen, Can Ince and Jan Bakker

Department of Intensive Care, Room HS3.20, Erasmus MC University Medical Centre Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands

Corresponding author: Prof. Jan Bakker, [email protected]

Published: 30 November 2009 Critical Care 2009, 13(Suppl 5):S13 (doi:10.1186/cc8011)This article is online at http://ccforum.com/content/13/S5/S13© 2009 BioMed Central Ltd

APACHE = Acute Physiology and Chronic Health Evaluation; HR = heart rate; ICU = intensive care unit; MAP = mean arterial pressure; NIRS =near-infrared spectroscopy; PFI = peripheral flow index; RincStO2 = rate of tissue oxygen saturation increase; SOFA = Sequential Organ FailureAssessment; StO2 = tissue oxygen saturation; ScvO2 = central venous oxygen saturation.

persistence of StO2 <70% on the SOFA and APACHE IIscores. We used the linear mixed-model analysis to assessthe magnitude of contribution from each systemic andperipheral physiological variable on all repeated StO2measurements during the 8-hour period of resuscitation.P !0.05 was considered statistically significant.

ResultsPatients’ demographic data are summarized in Table 1. Alldata used in the analysis were obtained at 2 hours, 4 hours,6 hours and 8 hours after admission.

To explore the relationship between changes of StO2 and theseverity of organ dysfunction, we stratified patients accordingto the evolution of StO2 levels within the 8-hour period of ICUresuscitation. Upon ICU admission, 12 (54%) patients hadlow StO2 levels. From these 12 patients, two patientsshowed normalization of the StO2 levels. All patients admittedwith normal StO2 still had a normal StO2 at 8 hours ofresuscitation. A total of 10 patients therefore persisted withlow StO2 and 12 patients with normal StO2 levels after the8 hours of ICU resuscitation (Figure 1).

Figure 2 shows the SOFA and APACHE II scores stratifiedby the groups after 8 hours of resuscitation. The mean scoresfor both SOFA and APACHE II scores were significantlyhigher in patients who persisted with low StO2 levels than inthose who exhibited normal StO2 levels 8 hours after theresuscitation period (P <0.05; median (interquartile range):APACHE II score, 32 (24 to 33) vs. 19 (15 to 25); SOFAscore, 8 (7 to 11) vs. 5 (3 to 8)) (Figure 2). Multiple

regression analysis on low StO2 levels adjusted for globalhemodynamic variables (HR, MAP and central venouspressure) showed that low StO2 levels had a significantcontribution for the prediction of SOFA score (regressioncoefficient = 3.0, 95% confidence interval = 2.2 to 5.7;P = 0.04) and APACHE II score (regression coefficient = 9.1,95% confidence interval = 3.3 to 13; P = 0.026).

The relationship between all repeated StO2 measurementsduring the 8-hour period of resuscitation with standard hemo-dynamic variables and with peripheral circulation parameterswas assessed using the mixed-model analysis to furtherexplore the contribution from each of these variables on theStO2 level. Table 2 presents the estimation coefficient fromeach variable. There was no significant relationship betweenStO2 and global hemodynamic variables. There was a strongassociation, however, between StO2 and clinical abnor-malities of peripheral perfusion, the PFI and RincStO2. Table 3presents the descriptive analysis of global hemodynamicvariables and peripheral circulation parameters stratified bythe level of StO2 at admission and after 8 hours. In patientswho received vasopressor therapy during resuscitation(number of patients = 16; number of StO2 measurements =64), the dose of vasopressor (noradrenaline) did not differbetween low (n = 35) and normal (n = 29) StO2 levels(P = 0.13; median (interquartile range): 0.19 (0.10 to 0.33)vs. 0.13 (0.06 to 0.25) µg/kg/minute).

Although there was no difference in admission lactate levelsbetween patients with low and normal StO2 levels (P = 0.34;median (interquartile range): 3.6 (2.2 to 6.0) vs. 3.4 (3.0 to



Table 1

Patient demographic data

Number of patients 22

Age (years) 62 (57 to 71)

Male/female 16/6

Sequential Organ Failure Assessment score 7 (5 to 9)

Acute Physiology and Chronic Health Evaluation II score 23 (16 to 30)

Admission category

Septic shock 3 pneumonia, 3 abdominal sepsis, 1 meningitis

Circulatory failure not associated with sepsis 3 hypovolemic/hemorrhagic, 3 cardiogenic, 4 postoperative, 2 trauma

Without circulatory failure or sepsis 1 cerebrovascular accident, 2 postoperative

Noradrenaline use 16 (72%)

Noradrenaline dose (µg/kg/minute) 0.16 (0.07 to 0.24)

Dobutamine use 8 (36%)

Dobutamine dose (µg/kg/minute) 4.3 (3.6 to 6.3)

Mechanical ventilation 15 (68%)

Survivor/nonsurvivor 17/5

Data expressed as number, as median (25th to 75th percentile), or as n (%).

Patients with circulatory failure (increased lactate) enrolled in EGDT protocol (8 hours) immediately following admission


n=22

n=2 n=6

n=8

n=8 n=6

n=14 2 hours

8 hours

abnormal peripheral perfusion normal peripheral perfusion

50%50%

29% 13%

Mortality 0% 0%

StO2 ±60% StO2 ±80%


Clinical significance of low StO2 in patients with shock

patients with abnormal peripheral circulation following EGDT have more organ failure


Admission Evolution during first 24h ICU mortality

StO2 n=221

StO2 n=221

StO2 n=221

StO2 n=221

Normal(>75%) n=181

Normaln=160

15%Normal(>75%) n=181 Abnormal

n=2157%

Abnormal(<75%) n=40

Normaln=15 13%Abnormal

(<75%) n=40 Abnormaln=25

56%

Dynamics of StO2mortality

Odds for mortality: persistent low StO2 during first 24h 7.9 (CI: 3-‐21, P<0.001)Odds for mortality: when StO2 decreased to <75% during first 24h 7.1 (CI: 2-‐21, P<0.001)Odds for mortality: persistent low StO2 and low peripheral perfusion 9.9 (CI: 3-‐41ß, P<0.001)


Peripheral and microcirculatory perfusion abnormalities following out-of-hospital cardiac arrestMichel van Genderen et al. Crit Care Med 2012 (in press)


Peripheral and microcirculatory perfusion abnormalities following out-of-hospital cardiac arrestMichel van Genderen et al. Crit Care Med 2012 (in press)

Conclusions: Following out-of-hospital cardiac arrest, the early post-resuscitation phase is characterized by abnormalities in sublingual microcirculation and peripheral tissue perfusion, which are caused by vasoconstriction due to induced systemic hypothermia and not by impaired systemic blood flow. Persistence of these alterations is associated with organ failure and death, independent of systemic hemodynamics.


Abnormal peripheral perfusioneffect of a stepwise increasing dose of NTG

Values are expressed as median [25th-75th] § * P<0.05 vs. TBL1 and TBL2

Tbaseline Tmax Tend

Capillary refill time, sec9

[8-12]

4 *

[4-6]

7*

[4-10]

Perfusion index, %0.7

[0.4-1.8]

2.7 *

[2.1-3.0]

1.6 *

[1.1-2.0]

Tskin-difference, 0C3

[2.1-3.4]

0.8 *

[-1.1-1.4]

1.4 *

[0.8-2.0]

StO2 (%)77

[64-82]

85 *

[74-92]

83

[73-88]


Conclusions

‣ Core and peripheral temperature relate to peripheral perfusion by vascular tone

‣ Peripheral perfusion is related to peripheral tissue oxygenation and microcirculatory function by vascular tone

‣ Abnormal peripheral perfusion is related to

• decreased lactate clearance

• increased organ failure and mortality

‣ Peripheral perfusion can be improved by NTG

‣ Patient outcome after improving peripheral perfusion is unknown


Date post:	09-Jul-2020
Category:	Documents
Upload:	others
View:	1 times
Download:	0 times

(Peripheral) Temperature and microcirculation · the microcirculation [1, 2, 3]. In addition, it...

Documents