Review of all current lit (Annals Emerg Med 2006;48(1):28)
Loma Linda Toolkit from Nguyen (http://www.llu.edu/llumc/emergency/patientcare/)
ICU Sepsis Screen
The
hallmark clinical manifestations of both sepsis and SIRS are two or more of the
following conditions:
2 or more SIRS plus infection
from the ancient Greeks, who used “sepsis” to describe putrefaction and a bad smell
Sepsis c organ dysfunction, hypoperfusion, hypotension, AMS, acidosis, oliguria, ARDS
pathogens in the blood stream
Hypotension after 2L of fluid
PaO2/FiO2<200
B pulmonary infiltrates
PAWP<18
Bone’s criteria define septic shock as systolic BP <90 mm Hg or >40-mm drop in standard BP; organ perfusion based on mean arterial BP, which is determined by diastolic, not systolic, BP; patients whose BP usually 170/100 mm Hg who present with BP of 110/60 mm Hg have septic shock (ie, >40-mm Hg drop in baseline BP; do not treat with fluids); precipitous drop in mean arterial BP causes change in mental status, hemodynamic embarrassment, renal dysfunction, gastrointestinal (GI) tract hypoperfusion, and liver hypoperfusion (DeBlieux)
hypoxemic hypoxia (low paO2)
Anemic Hypoxia
Stagnant Hypoxia (low CO)
Cytopathic Hypoxia (Cell machinery can not use O2)
In early sepsis, we pour in the fluids as proven by EGDT studies
AFter the resus period, fluid management is very different
Pts have a normal or supranormal oxygen delivery. Even after fluids and blood, pts may have decreased MAPs; the temptation is to keep administering fluids, but this is often counterproductive.
Fluids can be harmful:
Normal ICU care gives patients a ton of extraneous fluid already--med infusions
Figure
1 Cardiac output (CO) [and, similarly, venous return] depend on Pra. However,
this relationship depends critically on where the heart is operating on its
function curve. For example, when the heart is at point A, small increments in
Pra raise cardiac output greatly. In contrast, augmenting Pra when the heart is
at point B has little impact on cardiac output.
Figure
2. Venous return function curve superimposed on the cardiac function curve. For
this heart, the current state is described by the intersection point of the
cardiac function and venous return function curves (arrow 1). Raising mean
systemic pressure (for example, by infusing fluids or raising the legs) shifts
the venous return function curve rightwards. The new state (higher Pra and
higher cardiac output) is represented by the new intersection point (arrow 2).
Dynamic Measures
Spont inspiration will transiently raise the transmural Pra and shift CO curve to the left, increasing CO
Passive Mech Vent Inspiration shifts the CO curve to the right and temporarily decreases CO
Figure
3. The effect of spontaneous breathing is to shift leftwards the cardiac
function curve (solid line to dotted line), shifting the intersection point from
arrow 1 (end-expiration) to arrow 2 (end-inspiration). When the heart is
operating on the steep portion of the cardiac function curve (top, a),
this leftward shift moves the intersection point significantly (ie, Pra
falls and cardiac output rises). However, if cardiac function is depressed or
the circulation is fluid loaded (bottom, b), the respiratory shift
(from arrow 1 to arrow 2) has only a trivial impact on Pra and cardiac output.
Figure
4. Passive ventilation shifts the cardiac function curve rightwards. The solid
line represents end-expiration (intersection point 1), and the dotted line
end-inspiration (intersection point 2). If the heart is preload responsive (top,
a), the intersection point shifts and the resulting decrease in cardiac
output will reveal itself in changing pulse pressure, stroke volume, and aortic
or brachial artery peak flow velocity. If the heart is not preload responsive (bottom,
b), there will be little respiratory-related decrease in cardiac output
(as the intersection point shifts from arrow 1 to arrow 2).
Figure
5. Relationship of arterial pressure wave and passive respiration. Compared to
end-expiration, the systolic pressure and pulse pressure rise during inspiration
(INSP), then fall during expiration. PPmax = maximal pulse pressure; PPmin =
minimal pulse pressure.
Recommendations for Fluid Management in Severe Sepsis
|
Table 3. How To Measure PPV*
|
* See Figure 5 legend for expansion of abbreviations.
We summarize here our recommendations for management of fluids in septic
patients (Table
2 ). In the first 6 h of acute resuscitation, fluids should be infused
urgently to restore perfusion, guided by the ScvO2. Although infusing fluid
until the Pra reaches 8 to 12 mm Hg is commonly recommended, the only basis for
this is expert opinion.1281
We are concerned that excessive focus on Pra will lead to underresuscitation or
overresuscitation, emphasize again that ScvO2 should be the target, and
recommend that dynamic predictors be used (even at this early time) to gauge the
likely impact of fluids.
Once the patient has been resuscitated, fluid infusion should be ceased and
no maintenance fluids should be prescribed. The intravascular and total body
volume state should be judged periodically (daily in a rather stable patient,
more frequently in the newly admitted or unstable patient) using conventional
means such as clinical examination, intake and output records, changes in
weight, adequacy of urine output and perfusion, and other measures. Generally,
such assessment should be followed by diuretic administration because the
typical septic patient is hypervolemic. When persistent or recrudescent
hypotension, tachycardia, or oliguria raise the question as to whether fluids
would be helpful, the intensivist should estimate the probability of harm from a
fluid bolus. For many patients, the risks of fluid expansion are trivial and, in
such a case, an adequate fluid bolus should be infused rapidly while measuring
clinically relevant outcomes. For others, however, the risks of fluid infusion
may be real. Pulmonary or cerebral edema, abdominal compartment syndrome, acute
right-heart strain, or oliguria are all conditions that raise the potential
risk. Especially when these conditions are present, the clinician should attempt
to identify patients unlikely to benefit from fluids, in order to spare them
potential harm.
Depending on the monitoring available (arterial line, PAC, ScvO2,
echocardiography, Doppler ultrasound), one of the dynamic predictors of fluid
responsiveness should be used to guide any fluid therapy. Most often this will
involve PPV, as described in
Table 3 . Technology is available to display PPV, but care must be taken
that the preconditions for reliable measurement are adhered to (passive patient,
tidal volume of 8 to 12 mL/kg, regular rhythm). The patient must be assessed
carefully for respiratory activity, taking into account the ventilator pressure
and flow waveforms, hemodynamic tracings, and the clinical examination. We
recommend that the arterial pressure wave be printed on paper, preferably along
with measures of airway pressure or chest volume, for careful assessment and
measurement of pulse pressures. Visually and with the aid of a ruler, we find
the tallest and shortest pulse waves, ensuring that these represent the typical
cyclic pattern in a long strip. Further, it is essential to be certain that the
cardiac rhythm remains regular, especially when choosing values of minimum and
maximum pulse pressure. We then simply measure the pulse heights in millimeters
on a ruler because there is no need to perform the arithmetic in millimeters of
mercury. The equation for calculating PPV is provided in
Table 3.32
If the PPV is > 13%, a fluid bolus should be administered. Some reliable
indicator of perfusion should be measured before and after the bolus in order to
determine the effect. If the bolus is effective, the patient should be assessed
again for fluid responsiveness, and the procedure repeated until dynamic
measures predict no further response. If the initial bolus is not effective, the
intensivist should ask whether this is because the bolus was inadequate or the
patient is simply unresponsive to fluid.
Retrospective study showed 6% absolute mortality benefit to pts who received abx that covered the bugs within 60 minutes (Crit Care Med 2006;34:1589)
time to abx from outset of hypotension is assoc with mortality
Trends of vital signs are not sufficient endpoints to determine an adequate
response to therapy. Rady et al114 showed that 31 of 36 patients presenting with
shock and resuscitated to normal vital signs continued to have global tissue
hypoxia, as evidenced by decreased ScvO2 and increased lactate levels. A post
hoc analysis of the early goal-directed therapy study5 in patients with mean
arterial pressure greater than 100 mm Hg showed that control patients with
persistently abnormal ScvO2 and lactate levels at 6 hours had a significantly
higher mortality rate compared with the early goal-directed therapy patients
whose values had reached therapeutic goals (60.9% versus 20.0%, P<.05).122 Other
studies have also showed that a persistently high lactate is associated with
increased mortality.74, 77, 123 and 124 Therefore, continuous ScvO2 and serial
lactate measurements during resuscitation may help identify patients requiring
continued intensive therapy.
114 114 M.Y. Rady, E.P. Rivers and R.M. Nowak, Resuscitation of the critically ill in the ED responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate, Am J Emerg Med. 14 (1996), pp. 218–225. SummaryPlus | Full Text + Links | PDF (850 K) | Abstract + References in Scopus | Cited By in Scopus
Critical Care Medicine Volume 36(1), January 2008, pp 296-327
Surviving Sepsis Campaign Explanations (Crit Care Med 2004;32(11) suppl Nov 2004)
correct microcirculatory flow abnormalities through
Statins in the intensive care unit.
Curr Opin Crit Care. 2006 Aug;12(4):309-14
Association of statin therapy and increased survival in patients with multiple
organ dysfunction syndrome.
Intensive Care Med. 2006 Aug;32(8):1248-51.
Statins and sepsis.
Lancet. 2006 May 20;367(9523):1651
Review
Brit J Anaes 2007;98(2):163
Serum Lactate as a Predictor of Mortality in Emergency Department Patients with
Infection (Ann of Emerg Med 2005;45(5):524-528)
Early lactate clearance assoc c decreased mortality and apache II (crit care med 2004;32(8):1637)
Blueprint for Sepsis (Acad Emerg Med 2005;12(4):352)
Beth Israel Deaconess Medical Center: Boston, MA
CONCLUSIONS: The serum lactate level shows initial promise as a predictor of death in patients with infection, and may be useful as a risk stratification tool. Continued enrollment and the addition of clinical variables will assist in risk assessment. Further study is necessary to determine if early lactate-guided intervention can alter outcome.
As lactate increases from 2.0 to 8.0, mortality increases from 10-90% (Crit Care Med 1992;20:80)
venous and arterial is essentially equivalent in the ed population (Acad Emerg Med 1996;3:730)
but another article (1: Ann Emerg Med. 1997 Apr;29(4):479-83) suggests only real if low.
Lactate predicts death regardless of shock/organ failure (Crit Care Med Volume 37(5), May 2009, pp 1670-1677)
Even Lactates between 2-4 were predictive of mortality (Crit Care Med 2009 Vol. 37, No. 5,1670)
The prognostic value of muscle StO2 in septic patients (Intensive Care Medicine 2007;33(9))
River's Study (NEJM 345:19 11/8/01)
RCT—263 Patients
Post-ED Blinded
Control="Standard Care"
ARR Mortality 16%
NNT=~6 Patients
follow-up with rationale (Chest 2006;130:1579)
Also benefited post-op major surgery pts, though not in mortality (Crit Care 2005;9:R687)
Nguyen Retrospectively reviewed the feasibility of EGDT, steroids, and Xigris (Acad Emerg Med 2006;13(1):109)
Mortality benefit proven again by Trzeciak 1 year experience with egdt (Dellinger Chest 2006;129(2):225)
22 patients with 16 historical controls. Mortality rate 43% in pre group `8% in EGDT but not stat sig.
before and after review (Crit Care Med 2006;34:2707)
and another (Crit Care Med 2006;34:943)
Bryant's How to get it done (Acad Emerg Med 2007;14:1079)
$5000 less per patient due to decreased LOS (Shorr AF. CCM 2007;35(5) POLF)
More on it costing less (Crit Care Med 2007;35:1257) and (35:2090)=Dave Huang's
In another study, not cost-saving, but cost effective given QALY saved (Crit Care Med 2008;36:1168)
If SIRS and SBP<90 or Lactate >4
Central venous catheter capable of measuring central venous oxygen saturation (ScvO2)
A-Line
500-mL bolus of crystalloid every 30 minutes to achieve a CVP of 8-12 mm Hg
Vasopressors or vasodilators to achieve MAP > 65 mm Hg or < 90 mm Hg, respectively
If ScvO2 was < 70%, patients received red blood cell transfusions to achieve a hematocrit of at least 30%.
If at that hematocrit, ScvO2 was still < 70%, patients were infused an escalating dose of dobutamine to a maximum dose of 20 mcg/kg/min.
Patients then unable to achieve goals were intubated and ventilated
nguyen's study (Crit Care Med 2007;35(4):1105)
if entire bundle, mortality benefit
If using SvO2, 65% should be the target. (CCM Volume 32(7) July 2004 pp 1627-1628)
another prospective validation (Chest 2007;132:425)
intermittent sampling seems almost as good as cont. (Inten Care Med 2007;Online first Author Sakka SG)
Chest. 2007 Aug;132(2):425-32. Epub 2007 Jun 15. Links
Prospective external validation of the clinical effectiveness of an emergency
department-based early goal-directed therapy protocol for severe sepsis and
septic shock.
Jones AE, Focht A, Horton JM, Kline JA.
Assistant Director of Research, Department of Emergency Medicine, 1000 Blythe
Blvd, MEB 304e, Carolinas Medical Center, Charlotte, NC 28203, USA. alan.jones@carolinas.org
OBJECTIVE: To determine the clinical effectiveness of implementing early
goal-directed therapy (EGDT) as a routine protocol in the emergency department
(ED). METHODS: Prospective interventional study conducted over 2 years at an
urban ED. Inclusion criteria included suspected infection, criteria for systemic
inflammation, and either systolic BP < 90 mm Hg after a fluid bolus or lactate
concentration >/= 4 mol/L. Exclusion criteria were age < 18 years,
contraindication to a chest central venous catheter, and need for immediate
surgery. We prospectively recorded preintervention clinical and mortality data
on consecutive, eligible patients for 1 year when treatment was at the
discretion of board-certified emergency physicians. We then implemented an EGDT
protocol (the intervention) and recorded clinical data and mortality rates for 1
year. Prior to the first year, we defined a 33% relative reduction in mortality
(relative mortality reduction that was found in the original EGDT trial) to
indicate clinical effectiveness of the intervention. RESULTS: We enrolled 79
patients in the preintervention year and 77 patients in the postintervention
year. Compared with the preintervention year, patients in the postintervention
year received significantly greater crystalloid volume (2.54 L vs 4.66 L, p <
0.001) and frequency of vasopressor infusion (34% vs 69%, p < 0.001) during the
initial resuscitation. In-hospital mortality was 21 of 79 patients (27%) before
intervention, compared with 14 of 77 patients (18%) after intervention (absolute
difference, - 9%; 95% confidence interval, + 5 to - 21%). CONCLUSIONS:
Implementation of EGDT in our ED was associated with a 9% absolute (33%
relative) mortality reduction. Our data provide external validation of the
clinical effectiveness of EGDT to treat sepsis and septic shock in the ED.
New meta-analysis of "quantitative" therapies for sepsis showed benefit if early but none if done late. (Crit Care Med 2008;36:2734)
We should probably add on ScvCO2-SaCO2>6 as a marker for need for further resus after ScvO2>70 (Inten Care Med 2008;34:2218)
(Crit Care Med 2005;33(10):2194)
if you are not getting better, you are getting worse
baseline to day 1 improvement is the best predictor of outcome
MEDS Score
Crit Care Med 2007;35:192
Crit Care Med 2003;31:670
MEDS score was better than APACHE II for predicting mortality (Emerg Med J
2006;23:281-5)
Validated in SIRS patients (Crit Care Med 2008;36:421–6 )
e
|
Parameter |
Finding |
Points |
|
terminal illness |
absent |
0 |
|
|
present |
6 |
|
tachypnea or hypoxia |
respiratory rate <= 20 breaths per minute and oxygen saturation >= 90% |
0 |
|
|
respiratory rate > 20 breaths per minute and/or oxygen saturation <90% |
3 |
|
septic shock |
absent |
0 |
|
|
present |
3 |
|
platelet count |
>= 150,000 per µL |
0 |
|
|
< 150,000 per µL |
3 |
|
percent bands in differential count |
<= 5% |
0 |
|
|
> 5% |
3 |
|
age of the patient |
<= 65 years |
0 |
|
|
> 65 years |
3 |
|
lower respiratory tract infection |
absent |
0 |
|
|
present |
2 |
|
nursing home resident |
no |
0 |
|
|
yes |
2 |
|
mental status |
normal |
0 |
|
|
altered |
2 |
total score =
The higher the score, the more seriously ill the patient.
|
Total Score |
Risk Group |
Mortality Rate |
|
0 to 4 |
very low |
0.9 – 1.1% |
|
5 to 7 |
low |
2.0 – 4.4% |
|
8 to 11 |
moderate |
7.8 – 9.3% |
|
12 to 15 |
high |
16 – 20% |
|
16 to 27 |
very high |
39-50% |
Performance:
SIRS did not improve mortality but severe sepsis or septic shock did (Ann Emerg Med 2006;48:583)
|
||||||||||||||||||||||||
APACHE II = Acute Physiology and Chronic Health Evaluation II.
Early goal directed therapy 6-8
Drotrecogin alfa 16 (whole trial)
8 (APACHE II > 25)
Intensive insulin therapy 29
Low dose steroids 7
Daily hemodialysis 5.5
Additional Equipment for EGDT (Crit Care 2005;9:349)
Predisposition
Predisposition to respond to therapy
genetic comorbidities, environmental, social ie alcohol
Infection
Factors that may affect prognosis and likelihood of response to therapy
identifiable infection source, severity, localized-disseminated (eg bacteraemia)
organisms, appropriate/inappropriate initial antimicrobial therapy
Response
stratification of response based on: biomarkers conventional laboratory
parameters eg WBC, procalcitonin, CRP, lactate
Organ dysfunction
number of organ dysfunctions specific organ dysfunctions magnitude of each organ
dysfunction
Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International
Sepsis Definitions Conference. Crit Care Med 2003; 31:1250-1256
PIRO
After an infectious insult, endothelial damage occurs.
Activation of neutrophils
increased vascular permeability with resulting tissue edema
liberation of oxidants by the neutrophil.
Tissue factor (TF) is expressed by monocytes and the damaged vascular
endothelium
Inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and
interleukin (IL)-1 and IL-6, are secreted by the monocytes
Coagulation activation finally
release of thrombin and the formation of the fibrin clot
“Walling off” infection
Immune system overstimulation is not central
Cytokines may actually be beneficial in sepsis
Innate immune cells initiate responses via the Toll Like Receptors (TLR)
TLR 4 is part of a recognition complex for bacterial lipopolysaccharide
Modulation of tissue TLRs during the early phases of polymicrobial sepsis
correlates with mortality
Activation of nuclear factor kappaB a transcription factor involved in immediate
early gene activation during inflammation
Williams DL, Ha T, Li C, et al. Modulation of tissue Toll-like receptor 2 and 4
during the early phases of polymicrobial sepsis correlates with mortality. Crit
Care Med 2003; 31:1808-1818
Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med
2003; 348:138-150
Mental status changes – ANY KIND
Confusion/delirium/compativeness
Your pleasant grandpa is now pulling his lines out
Decreased responsiveness, pt is less perky
Lethargy
Tachypnea and/or tachycardia WITHOUT fever (yet)
Hypothermia – remember RECTAL temperature
Dropping (slightly initially) blood pressure – beware of RELATIVE changes
Your hypertensive granny with a BP of 100/82 may very well be septic
Rising blood sugar – increasing insulin requirements
? from circulating factors tnf, IL 1b
intrinsic cellular alterations
nitric oxide induced mitochondrial damage
depressed contractility with preserved or initially increased CO
dobutamine may help~15% of pts initially
septic cardiomyopathy
recovers at day 7-10 with no lasting damage
(inten care med 2006;32:799)
~60% of patients have sepsis induced hypokinesia (Crit Care Med 2008;36:1701)
Does the patient have a correctable source anywhere in his body?
Abscess
Liver
Brain
Retroperitoneum
Lung-mediastinum
Could the pleural effusion be an empyema?
Can the dilated kidney represent an obstructive pyelonephritis?
Are the paranasal sinuses/teeth filled with pus?
Is there any dead bowel in the abdomen?
Is the ascites infected?
Is the hematoma infected?
Is the gallbladder infected?
Has this organ perforated?
predicts microcirculatory changes and dobutamine reverses these changes in early sepsis (Intensive Care Medicine 2006;32:516)
shunting from stiffened endothelium closes down the microcirc. Increased cardiac output opens it back up
Any pt with sepsis and some evidence of organ dysfunction derives mortality benefit from aggressive early therapies (Critical Care 2005, 9:R607-R622)
MEDS Score mortality in ed sepsis score (Crit Care Med 2003;31(3):670)
Economics of EGDT protocol. This study states it is cheaper for the ED or hospital (Crit Care Med 2007;35:1257)
Bottom line: Hydrocortisone does not help in septic shock
European DB PRCT, 52 ICUs
1º outcome target decreased 28 day mortality in non-responders to ACTH (<9 rise)
2º outcome targets ICU and hospital mortalities, reversal of organ failures
Planned enrolment 800 patients to give a 80% power to detect a 10% reduction in mortality. Only 500 patients enrolled.
Inclusion Infection within 72 hours
2+ SIRS criteria
Evidence of shock despite fluids and vasopressors
Organ dysfunction
ACTH test required
Exclusion Prior steroids or immunosuppression
Dose of hydrocortisone: 50mg qid x4 days, 50mg bid x 3days, 50 mg once daily for 3 days
35 % of patients were medical
Source of infection was GI 49%, lungs 30%,
Non response to ACTH in 47% both groups
| 28 day mortality | Steroid | Placebo |
| All patients | 33.5% | 31% ns |
| Responders | 28.8% | 28.7% ns |
| Non-responders | 37.6% | Missed it but ns difference |
| Steroid | Placebo | |
| Reversal of shock | 80% | 74.6% p=0.14 |
| Median time to reverse shock - all patients | 3.1 days | 5.7 days p=0.003 |
| Median time to reverse shock - non-responders | 3.7 days | 6 days |
| Median time to reverse shock - responders | 2.8 days | ? |
| Secondary superinfection | 33% | 26.3% was sig |
| ICU neuropathy | 1% | 2% RR 0.5 (0.09-2.68) |
| Hyperglycemia >150 | 84% | 72% RR 1.17 (1.06-1.28) |
Conclusions: Hydrocortisone does not decrease mortality in septic shock
Does not increase reversal of shock but shock reverses quicker
No polyneuropathy increase
More superinfection
ACTH is test not useful
Hydrocortisone should not be routinely used in septic shock.
There may be a role in those still hypotensive after 1 hour. I've no idea why they suggest this.
Vasopressin in Septic Shock Trial
Bottom line; mortality decreased with low dose vasopressin only in patients with less severe sepsis
1º hypothesis - Low dose vasopressin -0.03units/min will decrease 28 day mortality from 60% to 50% in septic shock compared to norepinephrine alone
2º stratification - Severe septic shock = norepinephrine dose > 15 mcg/min
Less severe septic shock = norepinephrne 5-14 mcg/min
Resulted in 50% in each group
Inclusion Severe septic shock
SIRS criteria 2/4
Infection
1 organ dysfunction
Exclusion Septic shock > 24h, unstable heart, had received any vasopressin
Method Blinded infusion of vasopressin 0.01units/min or norepinephrine 5mcg/min
Titrated to MAP 65-75 mmHg
If vasopressin reached 0.03units/min or norepi 15mcg/min then other pressors were added
Results 396 randomised to vasopressin, 382 to norepi, all were equally sick with 2.5 organ failures and were on 20mcg/min norepi
Measured vasopressin was very low in the noprepi group and 80-100picomol/L in the vaso group
| 28 day mortality | Norepi | Vasopressin | p value |
| Total | 39.3% | 35.4% | 0.26 |
| More severe sepsis | 42.5% | 44% | 0.84 |
| Less severe sepsis | 35.7% | 26.5% | 0.04 |
90 day mortality, I couldn't write the numbers fast enough, but overall the difference in mortality was not significant p= 0.11 but the less severe sepsis group had a mortality of 46.1% with norepi, and 35.8% with vasopressin which was significant at p=0.04.
BP was similar in both groups
No difference in adverse events in both groups except small increase in digital ischemia in the vaso group with p= 0.06
early goal-directed resuscitation of the septic patient during the first
6 hrs after recognition (1B)
blood cultures prior to antibiotic therapy (1C)
imaging studies performed promptly to confirm potential source of
infection (1C)
administration of broad-spectrum antibiotic therapy within 1 hr of
diagnosis (1B)
reassessment of antibiotic therapy with microbiology and clinical data
to narrow coverage, when appropriate (1C)
a usual 7-10 days of antibiotic therapy guided by clinical response (1C)
source control with attention to the balance of risks and benefits of
the chosen method (1C)
administration of either crystalloid or colloid fluid resuscitation (1B)
aggressive fluid challenge to restore mean circulating filling pressure
(1C)
reduction in rate of fluid administration with rising filling pressures
and no improvement in tissue perfusion (1D)
vasopressor preference for norepinephrine or dopamine to maintain an
initial target of mean arterial pressure > 65 mm Hg (1C)
achieving a normal superior vena cava oxyhemoglobin saturation in the
presence of evidence of tissue hypoperfusion (1B)
dobutamine inotropic therapy when cardiac output remains low despite
fluid resuscitation and combined inotropic/vasopressor therapy (1C)
stress dose steroid therapy given only in septic shock after blood
pressure is identified to be poorly responsive to fluid and vasopressor
therapy (2C)
recombinant activated protein C in patients with severe sepsis and
clinical assessment of high risk for death (2B except 2C for
post-operative patients).
In the absence of tissue hypoperfusion, coronary artery disease, or
acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B)
a low tidal volume (1B) and limitation of inspiratory plateau pressure
strategy (1C) for acute lung injury (ALI)/acute respiratory distress
syndrome (ARDS)
application of at least a minimal amount of positive end-expiratory
pressure in acute lung injury (1C)
a semi-recumbent bed position unless contraindicated (1A)
avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A)
to decrease days of mechanical ventilation and ICU length of stay, a
conservative fluid strategy for patients with established ALI/ARDS who
are not in shock (1C)
protocols for weaning and sedation/analgesia (1B)
using either intermittent bolus sedation or continuous infusion sedation
with daily interruptions or lightening (1B)
avoidance of neuromuscular blockers, if at all possible (1B)
institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL
after initial stabilization ( 2C )
equivalency of continuous veno-veno hemofiltration or intermittent
hemodialysis (2B)
prophylaxis for deep vein thrombosis (1A)
use of stress ulcer prophylaxis to prevent upper GI bleeding using H2
blockers (1B) or proton pump inhibitors (1C)
and consideration of limitation of support where appropriate (1C).
(NEJM 2008;358(2):125)
Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis
Background The role of intensive insulin therapy in patients with severe
sepsis is uncertain. Fluid resuscitation improves survival among
patients with septic shock, but evidence is lacking to support the
choice of either crystalloids or colloids.
Methods In a multicenter, two-by-two factorial trial, we randomly
assigned patients with severe sepsis to receive either intensive insulin
therapy to maintain euglycemia or conventional insulin therapy and
either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES
200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate
of death at 28 days and the mean score for organ failure were coprimary
end points.
Results The trial was stopped early for safety reasons. Among 537
patients who could be evaluated, the mean morning blood glucose level
was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol
per liter]) than in the conventional-therapy group (151 mg per deciliter
[8.4 mmol per liter], P<0.001). However, at 28 days, there was no
significant difference between the two groups in the rate of death or
the mean score for organ failure. The rate of severe hypoglycemia
(glucose level, 40 mg per deciliter [2.2 mmol per liter]) was higher in
the intensive-therapy group than in the conventional-therapy group
(17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events
(10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates
of acute renal failure and renal-replacement therapy than was Ringer's
lactate.
Conclusions The use of intensive insulin therapy placed critically ill
patients with sepsis at increased risk for serious adverse events
related to hypoglycemia. As used in this study, HES was harmful, and its
toxicity increased with accumulating doses. (ClinicalTrials.gov number,
NCT00135473 [ClinicalTrials.gov] .)
analysis from SOAP study seems to show no increased mortality in pts receiving blood transfusions (Anesthes 2008;108:31)
National survey of ED directors and nursing directors (CCM 2007;35 POLF Carlbom DJ)
Infection + any two, get lactate
Temp >101 or <96.5
Altered Mental Status
Chills with Rigors
Tachy>90
RR>20
WBC>12000 or <4000
Sugar>120 mg/dl in absence of diabetes
signs of severe sepsis, any of the following distinct from the source of infection
SBP<90 or MAP<65 or SBP decrease > 40 from baseline
Cr > 2.0 or UO < 0.5 cc/kg/hour
Billi > 2 mg/dl
PLT < 100,000
Lactate >4
INR > 1.4 or PTT > 60
bilat infiltrates with criteria for ALI or need for increased supplemental
O2 to maintain SpO2>90
Intubating will increase the ScvO2
if it is low (Impact of emergency intubation on central venous oxygen
saturation in critically ill patients: a multicenter observational study
Critical Care 2009, 13:R63)