Goal-directed resuscitation in sepsis; a case-based approach

Transcription

1 Goal-directed resuscitation in sepsis; a case-based approach Jorge A Guzman, MD, FCCM Head, Section Critical Care Medicine Respiratory Institute Cleveland Clinic Foundation The challenges to managing septic shock are to find the right parameters to monitor and the endpoints for adequate resuscitation The hemodynamic status of critically ill patients is complex Complicating co-morbidities Conflicting therapeutic goals (hemodynamic instability and ALI/ARDS) 1

2 Response Early recognition Appropriate Antibiotics Early Goal Directed Therapy Injury Primary Organ Dysfunction Shock Resuscitation Secondary Organ Dysfunction SIRS Management of shock Recovery Glucose control Ventilatory support apc Days After Injury Recovery Progressive Organ Dysfunction Beal, AL. JAMA ; Goal-directed resuscitation Identify circulatory failure MAP < 65 mm Hg Lactate > 2 mmol/l Timing Global macrocirculatory goals MAP > 65 mm Hg Adequate preload Adequate urine output Microcirculatory goals ScvO 2 > 65-7% Lactate < 2 mmol/l Base excess Microcirculation assessment PCO 2 gap NIRS OPS UPSTREAM DOWNSTREAM 2

3 A 72 y/o male presented to the ED with increasing SOB, fever and cough. He has no significant PMH. His initial BP was 85/55 mm Hg. Mechanical ventilation was started due to poor response to O 2 supplementation via VM. He was resuscitated with 2 L on NS and sent to the MICU. An hour later his SBP remains in the 9s, he is making some urine, and he has received 3.5 L of NS thus far Physicians in the ICU continue administering intravenous fluids SSC guidelines for initial resuscitation Central venous pressure 8-12 mm Hg Mean arterial pressure (MAP) 65 mm Hg Urine output.5 ml kg-1 hr-1 Central venous (superior vena cava) or mixed venous oxygen saturation 7% or 65%, respectively (grade 1C) If ScvO 2 or SvO 2 of 7% or 65%, respectively, is not achieved with fluid resuscitation to the CVP target, then transfusion of PRBC to achieve a Htc of 3% and/or administration of a dobutamine infusion (up to a maximum of 2 μg kg-1 min-1) be used to achieve this goal (grade 2C). Crit Care Med 28; 36:

4 Volume resuscitation was sufficient Supplemental oxygen ± toendotracheal restore intubation ScvO and mechanical ventilation 2 of >7% in 36% of all patients Central venous and arterial catherization Sedation, paralysis (if intubated), or both 8-12 mm Hg 65 and 9 mm Hg No 7 mm Hg CVP ScvO 2 Goals achieved Yes MAP Hospital admission < 8 mm Hg < 65 mm Hg > 9 mm Hg < 7% Crystalloid Colloid Vasoactive agents Transfusion of red cells until hematocrit 3% Inotropic agents Engl J Med. 21;345: % < 7% Protocol Controls In-hospital mortality * 3.5 Protocol Controls * 33 Protocol Controls day mortality 49 6-day mortality 44 * 57 Mortality (%) EGDT; administered treatments Patients (%) IV fluids (L) IV Fluids EGDT Controls 6 hr prx 7-72 hr prx PRBC 6 hr prx 7-72 hr prx Percent (%) EGDT Controls Pressors -6 * Pressors 7-72 EGDT Standard Dobuta -6 9% of EGDT pts got nitroglycerin! * Dobuta 7-12 MV -6 MV 7-72 PAC -6 PAC 7-72 Rivers E. NEJM 21; 345: * 4

5 Normal BP may be misleading in sepsis Cryptic shock; patients with MAP > 1 mm Hg and serum lactate > 4 mmol/l Percent (%) 8 7 Should lactate, procalcitonin, or other 6 7 inflammatory markers be measured routinely? Initial ScvO2 Mortality (6 d) EGDT (n = 25) Controls (n = 23) Donnino, M et al. Chest 23;124,9S * Three hrs and 7L of fluids after ICU admission, his XR shows more congestion. The CVP is 9 mm Hg and the patient remains of high FiO 2 (8%), PEEP was increased to 1 cm H 2 O, and he is now on vasopressor support (norepinephrine 8 g/min). His Hb is 9.5 g/dl and his lactate remains elevated (4.4 mmol/l) Is CVP still a good preload indicator for this patient? 5

6 What to monitor? Preload Preload is defined as the load before contraction of the ventricle starts Static measures of preload CVP/RAP right ventricular preload PAOP left ventricular preload EDV - usually by echo Dynamic measures of preload Examine CV response to respiratory changes in pleural pressure, mainly in ventilated patients Give a fluid bolus and see what changes- the classical fluid challenge Static measures of preload There is NO correlation between blood volume and CVP 6

7 Crit Care Med 27; 35; 64 Intensive Care Med 24; 3: mm Hg CVP Responders Non responders 5% of critically ill patients may be loaded with fluids unnecessarily! Patients Definition of Responders N Challenge Responders Hemodynamic response to fluid loading Preisman S (25) Hofer CK (25) Swensen CH (26) Tavernier B (1998) Michard F (2) Michard F (23) Fessel M (25) Monnet X (25) Vallee F (25) Cardiac surgery Abdominal surgery Sepsis w/ circulatory failure Sepsis w/circulatory failure Septic shock circulatory failure Septic shock Septic shock Critically ill w/ circulatory failure Critically ill w/ circulatory failure >15% SV >35% SVI Increase in CO >15% SVI >15% >15% SVI >15% CI >15% in ABF (Doppler) >1% in SVI ml colloids 1 ml/kg (IBS) 6 % HES 25 ml/kg of Ringer 5-1mL 5 ml HES 5 ml HES 8 ml/kg HES 5 ml NS 4 ml/kg colloid x2 32/7 VLS (46%) 21 (6%) 4 (4%) 21/35 VLS (6%) 16 (4%) 32/66 VLS (48%) 13/22 VLS (59%) 2 (53%) 2 (39%) Heenan S (26) Critically ill w/ circulatory failure >15% in CO 21 1 L Ringer or 5 ml HES 9 (43%) Lafanechère A (26) Critically ill w/ circulatory failure >15% in ABF (Doppler) 22 PLR & 5 ml NS 1 (15%) 7

8 Fluid balance and outcomes CCM- 26;12:219 Ann Surg 23; 238:641 NEJM 26; 354:2564 If CVP is not the answer, then what? Arterial pressure variations during mechanical ventilation Reverse pulsus paradoxus Anesthesiology 25; 13:419 8

9 Quick bedside trick Small scale-high speed Large scale-slow speed What to monitor? Dynamic measures of preload- Arterial pressure variations Drawbacks No spontaneous breathing efforts Need larger tidal volumes (> 8mL/kg) Arrhythmias Assure accurate line recording (avoid bubbles, kinks, clots, etc) Does not work in patients with cor pulmonale - RVF Caution in CHF 9

10 What to monitor? Dynamic measures of preload- Response to a fluid challenge LV Output (SV, CO) Passive leg raising maneuver Normal Contractility Decreased Contractility Bolus Preload What to monitor? Dynamic measures of preload-passive Leg Raising Needs real time cardiovascular assessment (CO-CI) Ensure that there is a change in preload (CVP) before you call it negative Not affected by spontaneous breathing and arrhythmias SCARCE OUTCOME DATA 1

11 Five hours after ICU admission, MAP is 6 mm Hg on 3 mcg/min of NE. His CVP is 1 mm Hg and no longer fluid responsive. He remains mechanically ventilated requiring high FiO 2 (.6) and high PEEP and has minimal urine output. ScvO 2 is 62% and serum lactate is 4.2 mmol/l Is it time to know his cardiac output? 11

12 Number of trials What to monitor? Stroke volume and cardiac output 4 MAP goals in Sepsis Trials Misuse of CO may worsen outcomes 3 2 CVP goals in Sepsis Trials 3 Hayes et al. Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients. NEJM 1994;33: It would be of value if it guided therapies to improve outcomes Trial MAP goal Number of trials Trial CVP goal Number of trials CI goals in Sepsis Trials Number of trials 3 PAOP goals in Sepsis Trials Trial CI goal Trial PAOP goal Crit Care 27; 11 R67 To Swan or not to Swan? 12

13 What to monitor? Stroke volume and cardiac output Electric impedance/ reactance Partial CO 2 rebreathing Transthoracictransesophageal Echocardiography Cardiac output Arterial waveform analysis- Pulse contour (can also get SVV) Lithium indicator dilution Indirect Fick Thermodilution (PAC) Transpulmonary thermodiluton (can also get SVV-EVLW) The future: Intensivists assessing LVF using hand-held echo 6 hr of US training Blinded to the patient s clinical condition Correct interpretation Correct interpretation- Degree of LV failure Normal LVF 92% Mild-Moderate 69% Abnormal LVF 8% Severe failure 71% Melamed R et al. Chest 29; 135:

14 Six hours after ICU admission, MAP is 62 mm Hg on 22 mcg/min of NE and 5 mcg/min dobutamine. His CVP is 12 mm Hg and no longer fluid responsive. He remains mechanically ventilated with an FiO 2 of.6. Lactate is 3.5 mmol/l. Cardiac output obtained by pulse contour is 6. L/min Should we now focus on ScvO 2 and/or lactates as end-points of resuscitation? 14

15 Understanding ScvO 2 72 The difference between ScvO 2 and SvO 2 changes in shock ScvO 2 > SvO 2 by 5-8 %units What to monitor? Central venous oxygen saturation If Hb and SaO 2 are normal a low ScvO 2 /SvO 2 reflects a LOW OUTPUT state Oxygen Consumption Lactate SVO 2 (ScVO 2 ) BUT IT DOES NOT TELL YOU THE REASON Critical Oxygen Delivery Threshold VO 2 (SvO 2 - ScvO 2 ) Lactic acidosis Oxygen Delivery 15

16 Since metabolic demands vary widely in critically patients, there is NO NORMAL CARDIAC OUTPUT for critically ill patients Oxygen Consumption Lactate SVO 2 (ScVO 2 ) ScvO 2 may help decide whether additional interventions are necessary Oxygen Delivery A normal ScvO 2 does not indicate adequate perfusion in sepsis Treciak S et al. Critical Care 28;9(suppl):S2 16

17 Crit Care Med 1988; 16: Low venous oxygen saturation was infrequent in a Dutch study Mean ScvO ± 1.2%; mean lactate 2.7 ± 2.2 mmol/l. Mean CVP 9.8 ± 5.4 mm Hg. Only 1% (of septic shock pts) had a ScvO 2 < 5% van Beest et al. Critical Care 28; 12:R33 Venous saturation was high among patients in the Multiple Urgent Sepsis Therapies (MUST) protocol Baseline ScvO 2 in patients with septic shock (n 79) was 71 ± 12.3 % Shapiro NI et al, Crit Care Med 26; 34:

18 Dysoxia is present with normal or high ScvO 2 in septic ICU patients Resolved Global Tissue Hypoxia Lactate<2 mmol/l ScvO 2 >7% Moderate Global Tissue Hypoxia Lactate >2 mmol/l ScvO 2 <7% Severe Global Tissue Hypoxia Lactate >4 mmol/l ScvO 2 <7% High lactates with a high ScvO 2 Perel A, Intensive Care Med 28; 34:S65 Rivers EP, et al. Crit Care Med 27; 35:

19 Am J Surg 1996;171:221 Ann Emerg Med 25; 45:524-8 Hyperlactatemia; aerobic etiology relevant to sepsis Increased aerobic glycolysis by catecholamine stimulated Na + -K + ATPase hyperactivity (Lancet 25; 365:871) Paradigm shift Hyperlactatemia due to tissue hypoxia Mitochondrial may be the exception dysfunction and (Lancet not the 22; rule 36:219) Impaired Maypyruvate explain failed dehydrogenase trials aimingactivity (Shock 1996; 6:89) at supranormal DO 2 Sepsis-induced impaired lactate clearance (Am J Resp Crit Care Med 1998;157:121) 19

20 Crit Care Med 24; 32: Failure to normalize lactate carried a 1% mortality Clearing between hrs had a 42.5% mortality Patients clearing in <24 hr had a mortality of 4% Am J Surg 21; 182;481-5 The selection of hemodynamic parameters to monitor and end-points for resuscitation during septic shock is rarely straightforward! Hemodynamic management in shock Preload & Fluid responsiveness Cardiac function CO-SV- echo ScvO 2 Lactate Macrocirculation Microcirculation The complexity of critical illness and the presence of therapeutic conflicts (heart vs. lungs) necessitates monitoring of a combination of parameters 2

21 In summary Protocol driven early aggressive goal-directed resuscitation improve the outcome of patients in septic shock IF INITIATED EARLY Monitoring techniques that couple measurement of CO with ventilatory variations of systolic arterial pressure, pulse pressure, and SV enhance the ability to predict fluid responsiveness in circulatory failure Agreeing on end-points for resuscitation is difficult, but a combination of macro and microcirculatory targets seems likely to yield better results 21