Tag Archives: outcome

All Updates, ICU, PHARM, Resus, Ultrasound

Echo for cardiac arrest outcome prediction

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A meta-analysis of studies evaluation transthoracic echo as a means of predicting return of spontaneous circulation in cardiac arrest (ROSC) provides some likelihood ratios to what we already know: absence of sonographic cardiac activity means a very low chance of ROSC.

The authors report a pooled negative LR of 0.18 (95% CI = 0.10 to 0.31), and a positive likelihood ratio of 4.26 (95% CI = 2.63 to 6.92).

They conclude that focused transthoracic echo is a fairly effective (although not definitive) test for predicting death if no cardiac activity is noted during resuscitation, and recommend interpreting the echo in the light of the test characteristics and the clinical pre-test probability, as one should do for all imaging investigations:


“An elderly patient with an unwitnessed cardiac arrest already has very poor odds for survival. Confirmation of asystole on echo lowers those pretest odds by a factor of 5.6 and therefore might lead to termination of resuscitation. However, in the case of a 50-year-old rescued from drowning, detection of cardiac contractility on echo would increase his already fair odds of survival by a factor of 4.3, prompting continued aggressive resuscitation.”

Only five relatively small studies contributed to the findings. A more definitive answer to this question should be provided in the future by the multi-centre REASON 1 trial.

Objectives:  The objective was to determine if focused transthoracic echocardiography (echo) can be used during resuscitation to predict the outcome of cardiac arrest.

Methods:  A literature search of diagnostic accuracy studies was conducted using MEDLINE via PubMed, EMBASE, CINAHL, and Cochrane Library databases. A hand search of references was performed and experts in the field were contacted. Studies were included for further appraisal and analysis only if the selection criteria and reference standards were met. The eligible studies were appraised and scored by two independent reviewers using a modified quality assessment tool for diagnostic accuracy studies (QUADAS) to select the papers included in the meta-analysis.

Results:  The initial search returned 2,538 unique papers, 11 of which were determined to be relevant after screening criteria were applied by two independent researchers. One additional study was identified after the initial search, totaling 12 studies to be included in our final analysis. The total number of patients in these studies was 568, all of whom had echo during resuscitation efforts to determine the presence or absence of kinetic cardiac activity and were followed up to determine return of spontaneous circulation (ROSC). Meta-analysis of the data showed that as a predictor of ROSC during cardiac arrest, echo had a pooled sensitivity of 91.6% (95% confidence interval [CI] = 84.6% to 96.1%), and specificity was 80.0% (95% CI = 76.1% to 83.6%). The positive likelihood ratio for ROSC was 4.26 (95% CI = 2.63 to 6.92), and negative likelihood ratio was 0.18 (95% CI = 0.10 to 0.31). Heterogeneity of the results (sensitivity) was nonsignificant (Cochran’s Q: χ(2) = 10.63, p = 0.16, and I(2) = 34.1%).

Conclusions:  Echocardiography performed during cardiac arrest that demonstrates an absence of cardiac activity harbors a significantly lower (but not zero) likelihood that a patient will experience ROSC. In selected patients with a higher likelihood of survival from cardiac arrest at presentation, based on established predictors of survival, echo should not be the sole basis for the decision to cease resuscitative efforts. Echo should continue to be used only as an adjunct to clinical assessment in predicting the outcome of resuscitation for cardiac arrest.

Bedside Focused Echocardiography as Predictor of Survival in Cardiac Arrest Patients: A Systematic Review
Acad Emerg Med. 2012 Oct;19(10):1119-1126

Acute Med, All Updates, ICU, Kids, Resus

Etomidate & sepsis

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A meta-analysis attempts to quantify etomidate’s effect on mortality and adrenal suppression. Of course, we all know a meta-analysis can only be as reliable as the original data it’s analysing. I think editorialists Lauzier and Turgeon have a point with their statement:

“Given the widespread use of etomidate in the emergency room, we believe that a RCT designed to evaluate the safety of etomidate as a hypnotic agent for endotracheal intubation of patients with sepsis is not only ethical but also urgently warranted”

For a critique of the paper and subsequent discussion, check out the Academic Life in EM blog post by Brian Hayes


OBJECTIVE: To evaluate the effects of single-dose etomidate on the adrenal axis and mortality in patients with severe sepsis and septic shock.

DESIGN: A systematic review of randomized controlled trials and observational studies with meta-analysis.

SETTING: Literature search of EMBASE, Medline, Cochrane Database, and Evidence-Based Medical Reviews.

SUBJECTS: Sepsis patients who received etomidate for rapid sequence intubation.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We conducted a systematic review of randomized controlled trials and observational studies with meta-analysis assessing the effects of etomidate on adrenal insufficiency and all-cause mortality published between January 1950 and February 2012. We only examined studies including septic patients. All-cause mortality served as our primary end point, whereas the prevalence of adrenal insufficiency was our secondary end point. Adrenal insufficiency was determined using a cosyntropin stimulation test in all studies. We used a random effects model for analysis; heterogeneity was assessed with the I statistic. Publication bias was evaluated with Begg’s test. Five studies were identified that assessed mortality in those who received etomidate. A total of 865 subjects were included. Subjects who received etomidate were more likely to die (pooled relative risk 1.20; 95% confidence interval 1.02-1.42; Q statistic, 4.20; I2 statistic, 4.9%). Seven studies addressed the development of adrenal suppression associated with the administration of etomidate; 1,303 subjects were included. Etomidate administration increased the likelihood of developing adrenal insufficiency (pooled relative risk 1.33; 95% confidence interval 1.22-1.46; Q statistic, 10.7; I2 statistic, 43.9%).

CONCLUSIONS: Administration of etomidate for rapid sequence intubation is associated with higher rates of adrenal insufficiency and mortality in patients with sepsis.

Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis Crit Care Med. 2012 Nov;40(11):2945-53

All Updates, Resus, Trauma

Thoracoabdominal trauma outcomes

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In what the authors describe as ‘the largest and most rigorous description of blunt thoracoabdominal injury to date’, we learn some interesting things and are reminded of some others:

Most solid organ injuries in the abdomen are managed non-operatively

Thoracotomy – especially non-resuscitative thoracotomy – is rare

In patients with thoracoabdominal trauma, the overwhelming majority of injuries requiring operative intervention were found in the abdomen, therefore..

…excluding those patients in extremis requiring a resuscitative thoracotomy, the initial incision, without directive radiological information, belongs in the abdomen

Concomitant thoracic injury did not preclude nonoperative management of abdominal solid organ injury

This is a really interesting paper providing important data on the outcomes and management of a patient group that frequently produces management dilemmas in trauma centres.
The double jeopardy of blunt thoracoabdominal trauma
Arch Surg. 2012 Jun;147(6):498-504
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OBJECTIVES: To examine the specific injuries, need for operative intervention, and clinical outcomes of patients with blunt thoracoabdominal trauma.

DESIGN: Trauma registry and medical record review.

SETTING: Level I trauma center in Los Angeles, California.

PATIENTS: All patients with thoracoabdominal injuries from January 1996 to December 2010.

MAIN OUTCOME MEASURES: Injuries, incidence and type of operative intervention, clinical outcomes, and risk factors for mortality.

RESULTS: Blunt thoracoabdominal injury occurred in 1661 patients. Overall, 474 (28.5%) required laparotomy, 31 (1.9%) required thoracotomy (excluding resuscitative thoracotomy), and 1146 (69.0%) required no thoracic or abdominal operation. Overall incidence of intraabdominal solid organ injury was 59.7% and hollow viscus injury, 6.0%. Blunt cardiac trauma occurred in 6.3%; major thoracic vessel injury, in 4.6%; and diaphragmatic trauma, in 6.0%. The majority of solid organ injuries were managed nonoperatively (liver, 83.9%; spleen, 68.3%; and kidney, 91.2%). Excluding patients with severe head trauma, mortality ranged from 4.5% with nonoperative management to 18.1% and 66.7% in those requiring laparotomy and dual cavitary exploration, respectively. Age 55 years or older, Injury Severity Score of 25 or more, Glasgow Coma Scale score of 8 or less, initial hypotension, massive transfusion, and liver, cardiac, or abdominal vascular trauma were all independent risk factors for mortality.

CONCLUSIONS: Most patients with blunt thoracoabdominal trauma are managed nonoperatively. The need for non-resuscitative thoracotomy or combined thoracoabdominal operation is rare. The abdomen contains the overwhelming majority of injuries requiring operative intervention and should be the initial cavity of exploration in the patient requiring emergent surgery without directive radiologic data.

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Acute Med, All Updates, ICU, Resus

Not just in ARDS

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A ‘lung protective’ ventilation strategy that includes low tidal volumes has been shown to improve outcomes in patients with ARDS. Many also advocate it as sensible practice for any ventilated patient as a means of minimising the chances of ventilator-induced lung injury and hopefully improving outcome. A recent meta-analysis provides further evidence to support that recommendation:


Context Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS.

Objective To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS.

Data Sources MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012.

Study Selection Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations.

Data Extraction Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus.

Data Synthesis Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, −0.51; 95% CI, −0.70 to −0.32; I2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, −0.06 to 0.27; I2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results.

Conclusions Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation.

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome – A Meta-analysis
JAMA. 2012;308(16):1651-1659

Acute Med, All Updates, ICU, Resus

Hydroxyethyl Starch vs Saline

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Another nail in the coffin of starch solutions for critical care patients was banged in by Prof Myburgh and colleagues who published the results of the CHEST randomised trial this week(1). 7000 Australasian ICU patients received either 6% HES (130/0.4) in 0.9% saline (HES group) or 0.9% saline (saline group). There was no difference in mortality but there was more renal dysfunction, rash, and pruritis in the HES group.
This can be combined with another recent starch vs crystalloid paper demonstrating adverse outcomes from starch(2) to make the case that there is no role for these pharmaceuticals in resuscitation or critical care.
1. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care
N Engl J Med. 2012 Oct 17. [Epub ahead of print] Free Full Text
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Background The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported.

Methods We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy.

Results A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001).

Conclusions In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy

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2. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis
N Engl J Med. 2012 Jul 12;367(2):124-34
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BACKGROUND: Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.

METHODS: In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.

RESULTS: Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer’s acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer’s acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.

CONCLUSIONS: Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer’s acetate.

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Acute Med, All Updates, ICU, PHARM, Resus

What's with all the chloride? An assault on salt

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I continue to be bewildered at my ED colleagues’ overwhelming preference for 0.9% saline as a resuscitation fluid regardless of clinical presentation. However, I have to acknowledge a lack of robust high level clinical evidence demonstrating its relative harm compared with more balanced solutions such as Hartmann’s / Ringer’s lactate or one of the more scarcely available Plasma-Lyte solutions.
Human and animal studies have demonstrated that saline exacerbates hyperchloraemia and metabolic acidosis and has renal effects including renal vasoconstriction and decreased glomerular filtration rate. A large observational study on surgical patients suggested that saline therapy increases the risk of patients requiring acute dialysis compared with Plasma-Lyte administration(1).
A new study in JAMA provides some further clinical evidence that saline has harmful renal effects(2). It was a before-and-after observational study, in which the change was a restriction in chloride-rich fluids so that they were made available only after prescription by the attending specialist for specific conditions (eg, hyponatraemia, traumatic brain injury, and cerebral oedema). Four of the authors published another study on the metabolic effects of this changed fluid strategy, presumably on the same or an overlapping cohort of patients, which I blogged about here.
Significant findings were that the chloride-restrictive strategy was associated with a significantly lower increase in serum creatinine level during ICU stay, a decrease in the incidence of renal injury and failure (according to the RIFLE definitions), and a decrease in renal replacement therapy. These effects persisted after adjusting for known contributors to acute kidney injury.
As this is not a randomised trial cause and effect cannot be assumed, but this is consistent with other work.
In summary, keep pushing the saline if you want to increase your patients’ risk of acute kidney injury and the need for dialysis, whilst rendering them acidotic. You may even decrease their gut perfusion(3) and give them abdominal discomfort and subjective decreased cognitive ability(4). Alternatively, give Hartmann’s / Ringer’s lactate… although bear in mind that might not be such a good choice in the context of hyponatraemia, alkalaemia, cerebral oedema, or traumatic brain injury.
1. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte
Ann Surg. 2012 May;255(5):821-9
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OBJECTIVE: To assess the association of 0.9% saline use versus a calcium-free physiologically balanced crystalloid solution with major morbidity and clinical resource use after abdominal surgery.

BACKGROUND: 0.9% saline, which results in a hyperchloremic acidosis after infusion, is frequently used to replace volume losses after major surgery.

METHODS: An observational study using the Premier Perspective Comparative Database was performed to evaluate adult patients undergoing major open abdominal surgery who received either 0.9% saline (30,994 patients) or a balanced crystalloid solution (926 patients) on the day of surgery. The primary outcome was major morbidity and secondary outcomes included minor complications and acidosis-related interventions. Outcomes were evaluated using multivariable logistic regression and propensity scoring models.

RESULTS: For the entire cohort, the in-hospital mortality was 5.6% in the saline group and 2.9% in the balanced group (P < 0.001). One or more major complications occurred in 33.7% of the saline group and 23% of the balanced group (P < 0.001). In the 3:1 propensity-matched sample, treatment with balanced fluid was associated with fewer complications (odds ratio 0.79; 95% confidence interval 0.66-0.97). Postoperative infection (P = 0.006), renal failure requiring dialysis (P < 0.001), blood transfusion (P < 0.001), electrolyte disturbance (P = 0.046), acidosis investigation (P < 0.001), and intervention (P = 0.02) were all more frequent in patients receiving 0.9% saline.

CONCLUSIONS: Among hospitals in the Premier Perspective Database, the use of a calcium-free balanced crystalloid for replacement of fluid losses on the day of major surgery was associated with less postoperative morbidity than 0.9% saline.

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2. Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults
JAMA. 2012 Oct 17;308(15):1566-72
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CONTEXT: Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI).

OBJECTIVE: To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients.

DESIGN, SETTING, AND PATIENTS: Prospective, open-label, sequential period pilot study of 760 patients admitted consecutively to the intensive care unit (ICU) during the control period (February 18 to August 17, 2008) compared with 773 patients admitted consecutively during the intervention period (February 18 to August 17, 2009) at a university-affiliated hospital in Melbourne, Australia.

INTERVENTIONS: During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin.

MAIN OUTCOME MEASURES: The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) classification. Secondary post hoc analysis outcomes included the need for renal replacement therapy (RRT), length of stay in ICU and hospital, and survival.

RESULTS Chloride administration decreased by 144 504 mmol (from 694 to 496 mmol/patient) from the control period to the intervention period. Comparing the control period with the intervention period, the mean serum creatinine level increase while in the ICU was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P < .001), and the use of RRT was 10% (95% CI, 8.1%-12%; n = 78) vs 6.3% (95% CI, 4.6%-8.1%; n = 49) (P = .005). After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P < .001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge.
CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT.

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3. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients
Anesth Analg. 2001 Oct;93(4):811-6
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The IV administration of sodium chloride solutions may produce a metabolic acidosis and gastrointestinal dysfunction. We designed this trial to determine whether, in elderly surgical patients, crystalloid and colloid solutions with a more physiologically balanced electrolyte formulation, such as Hartmann’s solution and Hextend, can provide a superior metabolic environment and improved indices of organ perfusion when compared with saline-based fluids. Forty-seven elderly patients undergoing major surgery were randomly allocated to one of two study groups. Patients in the Balanced Fluid group received an intraoperative fluid regimen that consisted of Hartmann’s solution and 6% hetastarch in balanced electrolyte and glucose injection (Hextend). Patients in the Saline group were given 0.9% sodium chloride solution and 6% hetastarch in 0.9% sodium chloride solution (Hespan). Biochemical indices and acid-base balance were determined. Gastric tonometry was used as a reflection of splanchnic perfusion. Postoperative chloride levels demonstrated a larger increase in the Saline group than the Balanced Fluid group (9.8 vs 3.3 mmol/L, P = 0.0001). Postoperative standard base excess showed a larger decline in the Saline group than the Balanced Fluid group (-5.5 vs -0.9 mmol/L, P = 0.0001). Two-thirds of patients in the Saline group, but none in the Balanced Fluid group, developed postoperative hyperchloremic metabolic acidosis (P = 0.0001). Gastric tonometry indicated a larger increase in the CO2 gap during surgery in the Saline group compared with the Balanced Fluid group (1.7 vs 0.9 kPa, P = 0.0394). In this study, the use of balanced crystalloid and colloid solutions in elderly surgical patients prevented the development of hyperchloremic metabolic acidosis and resulted in improved gastric mucosal perfusion when compared with saline-based solutions.
IMPLICATIONS: This prospective, randomized, blinded trial showed that, in elderly surgical patients, the use of balanced IV solutions can prevent the development of hyperchloremic metabolic acidosis and provide better gastric mucosal perfusion compared with saline-based fluids.

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4. The effect of intravenous lactated Ringer’s solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers.
Anesth Analg. 1999 May;88(5):999-1003
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Animal studies have shown that large volumes of IV lactated Ringer’s solution (LR) decrease serum osmolality, thereby increasing cerebral water. These studies have led to recommendations to limit LR to avoid cerebral edema in neurosurgical patients. Eighteen healthy human volunteers aged 20-48 yr received 50 mL/kg LR over 1 h on one occasion and 0.9% sodium chloride (NS) on another. Venous samples were taken at baseline (T1), at infusion end (T2), and 1 h after T2 (T3). Time until first urination was noted. With LR, serum osmolality decreased by 4+/-3 mOsm/kg from T1 to T2 and increased insignificantly with NS. At T3, osmolality returned almost to baseline in the LR group. Blood pH increased from T1 to T2 with LR by 0.04+/-0.04 and decreased with NS by 0.04+/-0.04. These pH changes persisted at T3. Subjective mental changes occurred only with NS. Abdominal discomfort was more common with NS. Time until first urination was longer with NS (106+/-11 min) than with LR (75+/-10 min) (P < 0.001). In healthy humans, an infusion of large volumes of LR, but not NS, transiently decreased serum osmolality, whereas acidosis associated with NS persisted and urinary output was slower with NS.
IMPLICATIONS: Large volumes of lactated Ringer’s solution administered to healthy humans produced small transient changes in serum osmolality. Large volumes of sodium chloride did not change osmolality but resulted in lower pH.

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All Updates, PHARM, Resus, Trauma

What is 'hypotension' in penetrating trauma?

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I previously noted an article demonstrating that a ‘lowish’ – as opposed to a low – systolic blood pressure is a reason to be vigilant in blunt trauma patients, as a significant increase in mortality has been demonstrated with a systolic blood pressure (SBP) < 110 mmHg.
The same researchers have found similar results in patients with penetrating trauma.
Compared with the reference group with SBP 110-129mmHg, mortality was doubled at SBP 90-109mmHg, was four-fold higher at 70-89mmHg and 10-fold higher at <70mmHg. SBP values ≥150mmHg were associated with decreased mortality.
Systolic blood pressure below 110 mmHg is associated with increased mortality in penetrating major trauma patients: Multicentre cohort study
Resuscitation. 2012 Apr;83(4):476-81
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INTRODUCTION: Non-invasive systolic blood pressure (SBP) measurement is a commonly used triaging tool for trauma patients. A SBP of <90mmHg has represented the threshold for hypotension for many years, but recent studies have suggested redefining hypotension at lower levels. We therefore examined the association between SBP and mortality in penetrating trauma patients.

METHODS: We conducted a prospective cohort study in adult (≥16 years) penetrating trauma patients. Patients were admitted to hospitals belonging to the Trauma Audit and Research Network (TARN) between 2000 and 2009. The main outcome measure was the association between SBP and mortality at 30 days. Multivariate logistic regression models adjusted for the influence of age, gender, Injury Severity Score (ISS) and Glasgow Coma Score (GCS) on mortality were used. RESULTS: 3444 patients with a median age of 30 years (IQR 22.5-41.4), SBP of 126mmHg (IQR 107-142), ISS of 9 (IQR 9-14) and GCS of 15 (IQR 15-15), were analysed. Multivariable logistic regression analysis adjusted for age, gender, severity of injury and level of consciousness showed a cut-off for SBP at <110mmHg, after which increased mortality was observed. Compared with the reference group with SBP 110-129mmHg, mortality was doubled at SBP 90-109mmHg, was four-fold higher at 70-89mmHg and 10-fold higher at <70mmHg. SBP values ≥150mmHg were associated with decreased mortality.

CONCLUSION: We recommend that penetrating trauma patients with a SBP<110mmHg are triaged to resuscitation areas within dedicated, appropriately specialised, high-level care trauma centres.

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Acute Med, All Updates, ICU, Resus

Extracorporeal cardiopulmonary resuscitation

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You have a patient in cardiac arrest who has had excellent resuscitation from the point of collapse, and who has treatable underlying pathology (eg. PE or STEMI). However you’re unable to get return of spontaneous circulation so you call it. Someone just died for whom the technology exists to save them. Extracorporeal life support (ECLS) supports heart and lung function by externally providing circulatory flow and gas exchange until the patient’s underlying cause of arrest is treated or recovers.
ECLS requires an extracorporeal membrane oxygenation (ECMO) circuit to be placed during the cardiac arrest resuscitation. This may sound like extreme stuff, but there have been some amazing saves with this technology, and large numbers of in-hospital and out-of-hospital arrest patients have been treated in Japan, Korea, and Taiwan. ECMO has even been commenced in the field by prehospital emergency physicians.
An inspiring EMCrit podcast with Dr Joe Bellezzo described how this technology is applied at Sharp Memorial Hospital in San Diego. Bellezzo and colleagues have now published a series of their out-of-hospital arrest cases who received ECLS initiated by emergency physicians(1).
Coming back to the Japanese, a multicentre prospective cohort study of ECLS for out-of hospital cardiac arrest (the ‘SAVE-J’ study) selected patients with VF or pulseless VT in whom no ROSC was achieved with standard resuscitative measures. Their striking results mirror other ECLS studies and were published in abstract form in November 2011(2).
To me, the overwhelming take home messages from what I’ve seen and read on this are:


1. ECLS can provide dramatic saves with neurologically intact survival in cardiac arrest cases that otherwise would be dead.

2. The critical factor for successful clinical outcomes and avoidance of wasted resources and clinical futility is case selection. The underlying cause of arrest needs to be reversible (eg. myocarditis) or treatable (eg. STEMI) and good resuscitation needs to have been in place prior to ECLS.

3. In the right hospital with the right resuscitation team, it can be done.

1. Emergency physician-initiated extracorporeal cardiopulmonary resuscitation
Resuscitation. 2012 Aug;83(8):966-70
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CONTEXT: Extracorporeal cardiopulmonary resuscitation (ECPR) refers to emergent percutaneous veno-arterial cardiopulmonary bypass to stabilize and provide temporary support of patients who suffer cardiopulmonary arrest. Initiation of ECPR by emergency physicians with meaningful long-term patient survival has not been demonstrated.

OBJECTIVE: To determine whether emergency physicians could successfully incorporate ECPR into the resuscitation of patients who present to the emergency department (ED) with cardiopulmonary collapse refractory to traditional resuscitative efforts.

DESIGN: A three-stage algorithm was developed for ED ECPR in patients meeting inclusion/exclusion criteria. We report a case series describing our experience with this algorithm over a 1-year period.

RESULTS: 42 patients presented to our ED with cardiopulmonary collapse over the 1-year study period. Of these, 18 patients met inclusion/exclusion criteria for the algorithm. 8 patients were admitted to the hospital after successful ED ECPR and 5 of those patients survived to hospital discharge neurologically intact. 10 patients were not started on bypass support because either their clinical conditions improved or resuscitative efforts were terminated.

CONCLUSION: Emergency physicians can successfully incorporate ED ECPR in the resuscitation of patients who suffer acute cardiopulmonary collapse. More studies are necessary to determine the true efficacy of this therapy.

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2. Multicenter Non-Randomized Prospective Cohort Study of Extracorporeal Cardiopulmonary Resuscitation for Out-of Hospital Cardiac Arrest: Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J)
Circulation 2011; 124: A18132
[EXPAND Click for abstract]


Background: This study is aimed to examine the efficacy of extracorporeal cardiopulmonary resuscitation (ECPR) for patients in out-of hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT).

Method: The design of this study is a multicenter non-randomized prospective cohort study. Hypothesis is that the outcome of OHCA with VF or pulseless VT is similar between ECPR and conventional advanced life support (ALS). During from Oct. 2008 to Dec. 2010, forty six tertiary emergency hospitals were participated in this study. Patient inclusion criteria were 1) VF or pulseless VT on scene, 2) cardiac arrest on arrival at hospital, 3) within 45 minutes from a call to an arrival of hospital, and 4) non-ROSC by conventional ALS during 15 minutes after an arrival at hospital. Exclusion criteria were 1) age: 75 yr, 2) poor activities of daily livings, 3) non-cardiac verified cardiac arrest, and 4) hypothermia. According to the inclusion criteria, ECPR was adopted for OHCA in 26 hospitals (ECPR group) and conventional ALS was planned in 20 hospitals (non-ECPR group). Both groups (Intention-to-treat) were analyzed about the proportion of patients with favorable outcome (CPC1 or 2) assessed with the Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories at 1 month by chi square test and Fisher exact probability test.

Results: One hundred and eighty patients of ECPR group and 134 patients of non-ECPR group were enrolled. There was no difference between the background of ECPR group and non-ECPR group; Average age (56.0 VS 56.9), Witnessed (72.8% VS 75.4%), Lay-rescuer CPR (49.4% VS 45.5%), Acute coronary syndrome (65.6% VS 61.4%), Minutes from collapse to emergency department (26.8 VS 30.0). The favorable outcome rate in ECPR group (12.4%, 22 patients) was statistically higher than the rate in non-ECPR group (1.6%, two patients) (p<0.001).

Conclusion: Extracorporeal cardiopulmonary resuscitation may improve the outcome of out-of hospital cardiac arrest with VF or pulseless VT without ROSC by conventional ALS during 15 minutes after an arrival at hospital.

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Acute Med, All Updates, ICU, PHARM, Resus

Hypothermia after long down times

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You receive a patient resuscitated from cardiac arrest to a perfusing rhythm in your emergency department. History suggests a long ‘down time’: There was a ten minute duration of ‘no-flow’ (time from collapse to the start of resuscitation attempts).
Would this make you more likely or less likely to initiate targeted temperature management (TTM) and cool the patient to the recommended 32-34 degrees?
A recent study supports the suggestion that a longer no-flow time is associated with greater odds of survival with TTM compared with no TTM, than patients with shorter no-flow times. In other words, cooling the patient is more likely to make a difference in the ‘long down time’ patient, even though the overall survival in that group is obviously less.


Aim Mild therapeutic hypothermia has shown to improve long-time survival as well as favorable functional outcome after cardiac arrest. Animal models suggest that ischemic durations beyond 8 min results in progressively worse neurologic deficits. Based on these considerations, it would be obvious that cardiac arrest survivors would benefit most from mild therapeutic hypothermia if they have reached a complete circulatory standstill of more than 8 min.

Methods In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest, which remain comatose after restoration of spontaneous circulation. Data were collected from 1992 to 2010. We investigated the interaction of ‘no-flow’ time on the association between post arrest mild therapeutic hypothermia and good neurological outcome. ‘No-flow’ time was categorized into time quartiles (0, 1–2, 3–8, >8 min).

Results One thousand-two-hundred patients were analyzed. Hypothermia was induced in 598 patients. In spite of showing a statistically significant improvement in favorable neurologic outcome in all patients treated with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.14–1.93) this effect varies with ‘no-flow’ time. The effect is significant in patients with ‘no-flow’ times of more than 2 min (OR: 2.72; CI: 1.35–5.48) with the maximum benefit in those with ‘no-flow’ times beyond 8 min (OR: 6.15; CI: 2.23–16.99).

Conclusion The beneficial effect of mild therapeutic hypothermia increases with cumulative time of complete circulatory standstill in patients with witnessed out-of-hospital cardiac arrest.

The beneficial effect of mild therapeutic hypothermia depends on the time of complete circulatory standstill in patients with cardiac arrest
Resuscitation. 2012 May;83(5):596-601

Acute Med, All Updates, ICU, Kids, PHARM, Resus

Don't ignore the diastolic

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Most of us are pretty good at spotting hypotension and activating help or initiating therapy.
But ‘hypotension’ in many practitioners’ minds refers to a low systolic blood pressure. Who pays serious attention to the diastolic blood pressure? A low diastolic in a sick patient to me is a warning sign that their mean arterial pressure (MAP) is – or will be – low. After all, we spend about twice as long in diastole as in systole, so the diastolic pressure contributes more to the MAP than does the systolic.
A recent study showed that a low diastolic BP was one of several factors predictive of cardiac arrest on hospital wards: the most accurate predictors were maximum respiratory rate, heart rate, pulse pressure index, and minimum diastolic BP. These factors were more predictive than some of the variables included in the commonly used Early Warning Scores that trigger an emergency review.
The ‘pulse pressure index’ examined in the study is the pulse pressure divided by the systolic blood pressure (ie. [SBP-DBP]/SBP) which of course will be higher with lower diastolic blood pressures.
Importantly, the authors point out:


“In addition, our findings suggest that for many patients there is ample time prior to cardiac arrest to provide potentially life-saving interventions.”

…suggesting that there is still room for improvement in the identification and management of patients at risk for cardiac arrest, as the NCEPOD report ‘Cardiac Arrest Procedures: Time to Intervene?’ also showed.
They also recommend:


“…although systolic BP is commonly used in rapid response team activation criteria, incorporation of pulse pressure, pulse pressure index, or diastolic BP in place of systolic BP into the predictive model may be superior.”

Perhaps this may remind all of us to keep an eye on the diastolic as well as systolic BP when patients first present to us, and to include the importance of recognising diastolic hypotension in the teaching we provide our medical, paramedical and nursing students.

Predicting Cardiac Arrest on the Wards: A Nested Case-Control Study
Chest. 2012 May;141(5):1170-6 Free Full Text here
[EXPAND Click to read abstract]


Background: Current rapid response team activation criteria were not statistically derived using ward vital signs, and the best vital sign predictors of cardiac arrest (CA) have not been determined. In addition, it is unknown when vital signs begin to accurately detect this event prior to CA.

Methods: We conducted a nested case-control study of 88 patients experiencing CA on the wards of a university hospital between November 2008 and January 2011, matched 1:4 to 352 control subjects residing on the same ward at the same time as the case CA. Vital signs and Modified Early Warning Scores (MEWS) were compared on admission and during the 48 h preceding CA.

Results: Case patients were older (64 ± 16 years vs 58 ± 18 years; P = .002) and more likely to have had a prior ICU admission than control subjects (41% vs 24%; P = .001), but had similar admission MEWS (2.2 ± 1.3 vs 2.0 ± 1.3; P = .28). In the 48 h preceding CA, maximum MEWS was the best predictor (area under the receiver operating characteristic curve [AUC] 0.77; 95% CI, 0.71-0.82), followed by maximum respiratory rate (AUC 0.72; 95% CI, 0.65-0.78), maximum heart rate (AUC 0.68; 95% CI, 0.61-0.74), maximum pulse pressure index (AUC 0.61; 95% CI, 0.54-0.68), and minimum diastolic BP (AUC 0.60; 95% CI, 0.53-0.67). By 48 h prior to CA, the MEWS was higher in cases (P = .005), with increasing disparity leading up to the event.

Conclusions: The MEWS was significantly different between patients experiencing CA and control patients by 48 h prior to the event, but includes poor predictors of CA such as temperature and omits significant predictors such as diastolic BP and pulse pressure index.

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