Tag Archives: sepsis

Extreme white cell counts

Febrile children aged three months to three years with a white cell count over 25000/mm3 and fever were compared with controls whose leucoytosis was less extreme (15000-24999). The ‘extreme’ group had serious bacterial infection (SBI) in 39% compared with 15.4% controls. Pneumonia was the commonest SBI.
The authors conclude that in febrile children aged 3–36 months, the presence of extreme leucocytosis is associated with a 39% risk of having SBIs. The increased risk for SBI is mainly due to a higher risk for pneumonia. I conclude that leucocytosis is like fever: the cause may be benign, but the higher the number the less likely that is, even though the majority still won’t have SBI.
Extreme leucocytosis and the risk of serious bacterial infections in febrile children
Arch Dis Child. 2010 Mar;95(3):209-12

The right antibiotic in septic shock makes a massive difference

A retrospective review of appropriate vs inappropriate antimicrobial therapy was undertaken in over four thousand septic shock patients from multiple centres. In terms of definitions, the authors state:
Appropriate antimicrobial therapy was considered to have been initiated if an antimicrobial with in vitro activity appropriate for the isolated pathogen or pathogens (or in the case of culture-negative septic shock, an antimicrobial or antimicrobial agent concordant with accepted international norms for empiric therapy and modified to local flora) was either the first new antimicrobial agent with which therapy was started after the onset of recurrent or persistent hypotension or was initiated within 6 h of the administration of the first new antimicrobial agent. Otherwise, inappropriate therapy was considered to have been initiated.”
The results are striking: survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001).
A multivariable logistic regression analysis of possible factors that may affect outcome showed the appropriateness of the initial antimicrobial therapy remained most strongly associated with outcome (OR, 8.99; 95% CI, 6.60 to 12.23; p < 0.0001) among all the risk factors assessed.
Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock
Chest. 2009 Nov;136(5):1237-48
N.B. This work was done by the same authors who brought us the study that showed the earlier antibiotics were given to hypotensive septic patients, the better the outcome:
Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34:1589-1596

EGDT sepsis bundle challenged

An article in American Journal of Emergency Medicine by two intensivists challenges the science behind Rivers’ early goal-directed therapy (EGDT) protocol for severe sepsis / septic shock. In a nutshell:

  • Rivers’ study was small (n = 263), nonblinded, industry-supported and single-center
  • early fluids and antibiotics are a sound idea, but other components of EGDT are flawed
  • targeting a CVP is meaningless and could result in hypovolaemia or pulmonary oedema; dynamic markers of preload responsiveness such as pulse pressure variation or IVC diameter variation are better guides to fluid resuscitation
  • ScvO2 may be normal or elevated in septic shock patients; the low average ScvO2 in Rivers’ study has not been reproduced in subsequent studies.
  • packed cells have significant side effects and their non-deformability, pro-inflammatory and pro-thrombotic effects may impair microvascular perfusion and paradoxically worsen tissue oxygen delivery
  • dobutamine can potentially further worsen the haemodynamic status of patients with hypovolaemia, vasodilation, or a hyperdynamic circulation, which cannot be differentiated using CVP and ScvO2

Early goal-directed therapy: on terminal life support?
Am J Emerg Med. 2010 Feb;28(2):243-5
I like this paper, mainly because I have been uncomfortable with the chasing of arbitrary targets for some time. My own practice is to try to improve markers of organ hypoperfusion (such as lactate, urine output, mental status, and skin perfusion as well as blood pressure) by early antibiotics, fluid resuscitation guided by clinical and sonographic (IVC) signs, and vasoactive drugs guided by clinical and sonographic (basic echo) findings. I place a central venous catheter for access for the vasoactive drugs, rather than to get a CVP reading. I do measure ScvO2 with a central venous blood gas, but have rarely seen one below 70% even in severely shocked patients – I’m far more interested in clearing the lactate, as are these guys.

Bad news for etomidate from CORTICUS

In an a priori substudy of the CORTICUS multi-centre, randomised, double-blind, placebo-controlled trial of hydrocortisone in septic shock, the use and timing of etomidate administration was examined in relation to outcome.
Of 499 analysable patients, 96 (19.2%) received etomidate within the 72 h prior to inclusion. The proportion of non-responders to ACTH was significantly higher in patients who were given etomidate than in other patients (61.0 vs. 44.6%, P = 0.004). Etomidate therapy was associated with a higher 28-day mortality in univariate analysis (P = 0.02) and after correction for severity of illness (42.7 vs. 30.5%; P=0.06 and P=0.03) in two multi-variant models. Hydrocortisone administration did not change the mortality of patients receiving etomidate (45 vs. 40%).
Some of the previous attacks on etomidate have not been founded on the most rigorous evidence. However this study adds further to the difficulty in justifying etomidate’s use when a perfectly acceptable alternative (ketamine) exists for rapid sequence induction in the haemodynamically unstable septic patient.
The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock.
Intensive Care Med. 2009 Nov;35(11):1868-76

Identifying sick kids is still difficult

A systematic review to identify clinical features that have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings resulted in the calculation of likelihood ratios. Clinical features with a positive likelihood ratio of more than 5.0 were deemed red flags (ie, warning signs for serious infection); features with a negative likelihood ratio of less than 0.2 were deemed rule-out signs.
The features identified in several studies as red flags were :

  • Cyanosis (+LR range 2.66-52.20)
  • Rapid breathing (+LR 1.26-9.78)
  • Poor peripheral perfusion (+LR 2.39-38.80)
  • Petechial rash (+LR 6.18-83.70)]

In one primary care study the following were identified as strong red flags:

  • Parental concern (+LR 14.40, 95% CI 9.30-22.10)
  • Clinician instinct (+LR 23.50, 95 % CI 16.80-32.70)

Temperature of 40 degrees C or more had value as a red flag in settings with a low prevalence of serious infection.
What about ruling out serious illness?
Unfortunately, no single clinical feature had rule-out value but some combinations can be used to exclude the possibility of serious infection-for example, pneumonia is very unlikely (-LR 0.07, 95% CI 0.01-0.46) if the child is not short of breath and there is no parental concern.
An accompanying editorial sums up the challenge of paediatric emergency medicine in a nutshell:
“What is clear is that in 2010 we do not know how to effectively recognise or rule out severe disease in ill children and what is more, we do not even have a cohesive national or even global research strategy to address this problem.”
Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review.
Lancet. 2010 Mar 6;375(9717):834-45

Procalcitonin reduced antibiotic use

In a multicentre study in France, adult patients expected to stay in the intensive care unit for more than 3 days who had suspected bacterial infections were randomised to have antibiotics started or stopped based on predefined cut-off ranges of procalcitonin concentrations (n=307 patients) or to receive antibiotics according to present guidelines (control, n=314). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14∙3 days [SD 9·1] vs 11∙6 days [SD 8∙2]; absolute difference 2∙7 days, 95% CI 1∙4 to 4∙1, p<0∙0001) without a difference in 28-day or 60-day mortality or ICU length of stay.  An editorial points out that as an open-label trial, a treatment bias might have occurred because physicians were aware that their patients had had procalcitonin measurements taken, raising the question as to whether the procalcitonin concentrations themselves or simply the act of measuring procalcitonin led to the recorded reduction in antibiotic use.
The study used the following guidelines for starting, continuing, or stopping of antibiotics according to procalcitonin concentrations:
Guidelines for starting of antibiotics – Excludes situations requiring immediate antibiotic treatment (eg, septic shock, purulent meningitis)

  • Concentration <0·25 μg/L – Antibiotics strongly discouraged
  • Concentration ≥0·25 and <0·5 μg/L – Antibiotics discouraged
  • Concentration ≥0·5 and <1 μg/L – Antibiotics encouraged
  • Concentration ≥1 μg/L – Antibiotics strongly encouraged

If blood sample taken for calculation of procalcitonin concentration at early stage of episode, obtain a second procalcitonin concentration 6–12 h later
Guidelines for continuing or stopping of antibiotics

  • Concentration <0·25 μg/L – Stopping of antibiotics strongly encouraged
  • Decrease by ≥80% from peak concentration, or concentration ≥0·25 and <0·5 μg/L – Stopping of antibiotics encouraged
  • Decrease by <80% from peak concentration, and concentration ≥0·5 μg/L – Continuing of antibiotics encouraged
  • Increase of concentration compared with peak concentration and concentration ≥0·5 μg/L – Changing of antibiotics strongly encouraged

Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial
Lancet. 2010 Feb 6;375(9713):463-74

Lactate clearance goal in sepsis

Previous work in severe sepsis/septic shock patients has shown that a decrease in lactate concentration by at least 10% during emergency department resuscitation predicts survival. Since this is a potential alternative resuscitation goal to a central venous oxygen saturation (ScvO2) of 70% (as per surviving sepsis campaign guidelines), lactate clearance was compared with ScvO2 in a randomised non-inferiority trial of 300 patients.
All patients were managed in the ED and received fluids, antibiotics, and vasopressors as needed. Then lactate clearance or ScvO2 were measured, and if the respective goals of 10% or 70% were not met, packed cells or dobutamine were given depending on haematocrit. Lactate clearance was the percentage decrease in lactate between two venous specimens taken two hours apart.
Interestingly only 29 patients received either packed cells or dobutamine. Each group was similar in terms of time to antibiotic therapy and amount of fluid given. Patients in the group resuscitated to a lactate clearance of 10% or higher had 6% lower in-hospital mortality than those resuscitated to an ScvO2 of at least 70% (95% CI for this difference, –3% to 15%) exceeding the –10% predefined noninferiority threshold.
The authors conclude ‘these data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a computerized spectrophotometric catheter in the resuscitation of sepsis.’
Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial
JAMA. 2010 Feb 24;303(8):739-46

Chlorhexidine-alcohol surgical site prep

In contrast to the situation with skin preparation for intravascular catheters, there have been no recommendations for surgical practice. A randomised controlled trial compared chlorhexidine–alcohol (2% chlorhexidine gluconate and 70% isopropyl alcohol or ‘ChloraPrep’) with povidone–iodine in 849 patients undergoing surgery. The overall rate of surgical-site infection was significantly lower in the chlorhexidine–alcohol group than in the povidone–iodine group (9.5% vs. 16.1%) and chlorhexidine–alcohol was significantly more protective than povidone–iodine against both superficial incisional infections (4.2% vs. 8.6%) and deep incisional infections (1% vs. 3%) but not against organ-space infections (4.4% vs. 4.5%)
Chlorhexidine-Alcohol versus Povidone-Iodine for Surgical-Site Antisepsis
N Engl J Med. 2010 Jan 7;362(1):18-26

Noradrenaline vs Dopamine in Shock

Another nail in dopamine’s coffin? In a blinded randomised controlled trial in shocked patients1, there was no difference in mortality when dopamine was compared with noradrenaline as the initial vasopressor. However the dopamine group had a significantly higher incidence of dysrythmia. In addition, mortality was higher in the predefined subgroup of 280 patients with cardiogenic shock. The results of this European study of 1679 patients are very similar to those of a similar but open-label American trial in 252 patients published recently2.
1. Comparison of Dopamine and Norepinephrine in the Treatment of Shock
NEJM 2010;362(9):779-89
2. Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock
Shock. 2009 Oct 21. [Epub ahead of print]