Category Archives: Acute Med

Acute care of the medically sick adult

New STEMI guidelines

Primary percutaneous coronary intervention or fibrinolysis for STEMI? What if you don’t have PCI at your hospital?
The new 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction is out and you can get the summary here.
Here’s what they say about initial reperfusion therapy:

Onset of Myocardial Infarction: Recommendations
Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals
Class I
1. All communities should create and maintain a regional system of STEMI care that includes assessment and continuous quality improvement of emergency medical services and hospital-based activities. Performance can be facilitated by participating in programs such as Mission: Lifeline and the Door-to-Balloon Alliance.(Level of Evidence: B)
2. Performance of a 12-lead electrocardiogram (ECG) by emergency medical services personnel at the site of first medical contact (FMC) is recommended in patients with symptoms consistent with STEMI.(Level of Evidence: B)
3. Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours. (Level of Evidence: A)
4. Primary PCI is the recommended method of reper- fusion when it can be performed in a timely fashion by experienced operators. (Level of Evidence: A)
5. Emergency medical services transport directly to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI, with an ideal FMC-to-device time system goal of 90 minutes or less.(Level of Evidence: B)
6. Immediate transfer to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI who initially arrive at or are transported to a non–PCI-capable hospital, with an FMC-to-device time system goal of 120 minutes or less.(Level of Evidence: B)
7. In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non–PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 minutes because of unavoidable delays.(Level of Evidence: B)
8. When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival.(Level of Evidence: B)
Class IIa
1. Reperfusion therapy is reasonable for patients with STEMI and symptom onset within the prior 12 to 24 hours who have clinical and/or ECG evidence of ongoing ischemia. Primary PCI is the preferred strategy in this population. (Level of Evidence: B)

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation. 2012 Dec 17. [Epub ahead of print]

Externally rotate leg for femoral vein access

Want to access the femoral vein? Externally rotate the leg at the hip and things might be a bit easier. This study was done in adult patients, with the knee straight and no abduction applied. External rotation is also helpful in kids, with abduction up to sixty degrees.


Objective: To determine if external rotation of the leg increases the size and accessibility of the femoral vein compared with a neutral position.

Methods: One hundred patients presenting to a tertiary teaching hospital were prospectively recruited. The right common femoral vein of each subject was scanned with a linear probe (5–10 MHz) inferior to the inguinal ligament, with the leg in a neutral position and then in the externally rotated position. The transverse diameter of the femoral vein, the accessible diameter of the vein (lying medial to the femoral artery) and the depth of the vein were measured.

Results: The mean diameter of the femoral vein in the externally rotated leg was greater than with the leg in the neutral position (15.4 mm vs 13.8 mm); the mean difference was 1.6 mm (95% CI 1.3–1.9). The mean accessible diameter of the femoral vein was larger with the leg externally rotated (13.8 mm vs 11.7 mm, mean difference 2.1 mm, 95% CI 1.8–2.5). The depth from the skin to the femoral vein was less with the leg in external rotation (20.9 mm vs 22.6 mm, mean difference 1.7 mm, 95% CI 1.2–2.2). The mean diameter and depth were greater in patients with overweight or obese body mass index (BMI) measurements in both leg positions. The increase in femoral vein diameter and accessibility with external rotation was observed in all BMI groups.

Conclusion: The total and accessible femoral vein diameter is increased and the surface depth of the vein is decreased by placing the leg in external rotation compared with the neutral position.

Simple external rotation of the leg increases the size and accessibility of the femoral vein
Emerg Med Australas. 2012 Aug;24(4):408-13

Hyperglycaemia & mortality in sepsis – lactate dependent?

I like this paper for introducing a new concept to me. For years the critical care community has recognised the link between hyperglycaemia and mortality, leading to early recommendations of intensive insulin regimens subsequently shown not to be of benefit. Now it appears that the association between hyperglycaemia and mortality may be less relevant in patients with a normal lactate.
In a study of adult nondiabetic critically ill patients, hyperglycaemia had a significant association with increased mortality risk using simple univariate analysis. When they adjusted for concurrent hyperlactataemia however, hyperglycaemia was not significantly associated with increased mortality risk.
The authors discuss several known or postulated aspects of interplay between lactate and glucose in sepsis:

  • Hyperlactataemia appears to inhibit glucose uptake by muscle cells and decrease activity of the GLUT-4 transporters
  • Hyperlactataemia has also been shown to increase insulin resistance directly
  • Glucose and lactate levels tend to be elevated simultaneously in severe sepsis at baseline.
  • Experimentally it has been estimated that 45% of infused (radiolabelled) lactate is either converted into glucose via gluconeogenesis or is transformed into glycogen via the Cori cycle, representing a higher proportion of glucose formation from lactate than in nonseptic controls.
  • It is possible that elevated glucose and lactate levels in sepsis both may be measures of the same phenomenon: glucose accumulates due to the sympathomimetic response to a systemic infection with increased catecholamine levels leading to increased activity of the Na+K+-ATPase, resulting in accumulation of adenosine diphosphate (ADP). Increased levels of ADP in turn augment glycogenolysis.
  • Mitochondrial metabolism cannot meet the increased cellular energy needs of sepsis, resulting in accumulation of ADP and leading to cytosolic glycolysis and lactate production, even in an aerobic environment.

The augmented glycolysis of sepsis (and during adrenergic therapy such as epinephrine/adrenaline or albuterol/salbutamol) is one of the causes of a raised lactate to consider when applying the LACTATES mnemonic I like to use.
Hyperlactatemia affects the association of hyperglycemia with mortality in nondiabetic adults with sepsis
Acad Emerg Med. 2012 Nov;19(11):1268-75
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BACKGROUND: Admission hyperglycemia has been reported as a mortality risk factor for septic nondiabetic patients; however, hyperglycemia’s known association with hyperlactatemia was not addressed in these analyses.

OBJECTIVES: The objective was to determine whether the association of hyperglycemia with mortality remains significant when adjusted for concurrent hyperlactatemia.

METHODS: This was a post hoc, nested analysis of a retrospective cohort study performed at a single center. Providers had identified study subjects during their emergency department (ED) encounters; all data were collected from the electronic medical record (EMR). Nondiabetic adult ED patients hospitalized for suspected infection, two or more systemic inflammatory response syndrome (SIRS) criteria, and simultaneous lactate and glucose testing in the ED were enrolled. The setting was the ED of an urban teaching hospital from 2007 to 2009. To evaluate the association of hyperglycemia (glucose > 200 mg/dL) with hyperlactatemia (lactate ≥ 4.0 mmol/L), a logistic regression model was created. The outcome was a diagnosis of hyperlactatemia, and the primary variable of interest was hyperglycemia. A second model was created to determine if coexisting hyperlactatemia affects hyperglycemia’s association with mortality; the main outcome was 28-day mortality, and the primary risk variable was hyperglycemia with an interaction term for simultaneous hyperlactatemia. Both models were adjusted for demographics; comorbidities; presenting infectious source; and objective evidence of renal, respiratory, hematologic, or cardiovascular dysfunction.

RESULTS: A total of 1,236 ED patients were included, and the median age was 77 years (interquartile range [IQR] = 60 to 87 years). A total of 115 (9.3%) subjects were hyperglycemic, 162 (13%) were hyperlactatemic, and 214 (17%) died within 28 days of their initial ED visits. After adjustment, hyperglycemia was significantly associated with simultaneous hyperlactatemia (odds ratio [OR] = 4.14, 95% confidence interval [CI] = 2.65 to 6.45). Hyperglycemia and concurrent hyperlactatemia were associated with increased mortality risk (OR = 3.96, 95% CI = 2.01 to 7.79), but hyperglycemia in the absence of simultaneous hyperlactatemia was not (OR = 0.78, 95% CI = 0.39 to 1.57).

CONCLUSIONS: In this cohort of septic adult nondiabetic patients, mortality risk did not increase with hyperglycemia unless associated with simultaneous hyperlactatemia. The previously reported association of hyperglycemia with mortality in nondiabetic sepsis may be due to the association of hyperglycemia with hyperlactatemia.

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Etomidate & sepsis

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

Not just in ARDS

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

Hydroxyethyl Starch vs Saline

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

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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Infectious biomarkers in the critically ill

A study examining patterns of procalcitonin in a group of critically ill patients(1) showed some interesting findings:

Shock was associated with higher procalcitonin values independent of the presence of infection

Procalcitonin (PCT) levels were less in patients who developed infections later during their ICU stay compared with those who had infections when admitted to ICU.

The accompanying editorial(2) reminds us about commonly used inflammatory biomarkers.

White blood cells are influenced by almost every inflammatory stimulus, rendering them unhelpful in the management of severely ill patients.

Daily monitoring of CRP levels can identify ICU-acquired infections early, and some prognostic information can be provided by how rapidly CRP levels respond to treatment.

PCT rises early in severe sepsis, mainly by pneumonia and bloodstream infections, and can reflect the severity of the systemic inflammatory response syndrome to infection. PCT is more specific than CRP for infection compared with non-infectious causes of systemic inflammatory response syndrome. However PCT can also be increased in noninfectious diseases such as acute pancreatitis and cardiogenic shock.

1. Longitudinal changes in procalcitonin in a heterogenous group of critically ill patients
Crit Care Med. 2012 Oct;40(10):2781-2787
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OBJECTIVE: The utility of procalcitonin for the diagnosis of infection in the critical care setting has been extensively investigated with conflicting results. Herein, we report procalcitonin values relative to baseline patient characteristics, presence of shock, intensive care unit time course, infectious status, and Gram stain of infecting organism.

DESIGN: Prospective, multicenter, observational study of critically ill patients admitted to intensive care unit for >24 hrs. SETTING:: Three tertiary care intensive care units.

PATIENTS: All consenting patients admitted to three mixed medical-surgical intensive care units. Patients who had elective surgery, overdoses, and who were expected to stay <24 hrs were excluded.

INTERVENTIONS: Patients were followed prospectively to ascertain the presence of prevalent (present at admission) or incident (developed during admission) infections and clinical outcomes. Procalcitonin levels were measured daily for 10 days and were analyzed as a function of the underlying patient characteristics, presence of shock, time of infection, and pathogen isolated.

MAIN RESULTS: Five hundred ninety-eight patients were enrolled. Medical and surgical infected cohorts had similar baseline procalcitonin values (3.0 [0.7-15.3] vs. 3.7 [0.6-9.8], p = .68) and peak procalcitonin (4.5 [1.0-22.9] vs. 5.0 [0.9-16.0], p = .91). Infected patients were sicker than their noninfected counterparts (Acute Physiology and Chronic Health Evaluation II 22.9 vs. 19.3, p < .001); those with infection at admission had a trend toward higher peak procalcitonin values than did those whose infection developed in the intensive care unit (4.9 vs. 1.4, p = .06). The presence of shock was significantly associated with elevations in procalcitonin in cohorts who were and were not infected (both groups p < .003 on days 1-5).

CONCLUSIONS: Procalcitonin dynamics were similar between surgical and medical cohorts. Shock had an association with higher procalcitonin values independent of the presence of infection. Trends in differences in procalcitonin values were seen in patients who had incident vs. prevalent infections.

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2. The many facets of procalcitonin in the critically ill population
Crit Care Med. 2012 Oct;40(10):2903-5

Surgical treatment for acute massive pulmonary embolism

A recent paper reminds us that surgery is an option in the management of massive pulmonary embolism(1), to be considered in the patient for whom thrombolysis has failed or is contraindicated. Good outcomes were produced when surgery was performed in a centre capable of cardiopulmonary bypass (6% 30-day postoperative mortality), but is surgery an option when these facilities are unavailable?

The “venous inflow occlusion” technique involves clamping the venae cavae prior to removing clot directly from the pulmonary artery and its branches after median sternotomy, and can be performed in any hospital with surgical facilities. Under normothermic conditions, speed is of the essence once cardiac arrest occurs, since the irreversible anoxic cerebral injury will occur after just a few minutes.
Clarke and Abrams wrote in the Lancet in 1972(2):

Our use of venous inflow-occlusion has given results which compare well with those obtained with extracorporeal circulation. 50% of our patients survived. All patients who had emboli removed without an episode of ventricular asystole survived surgery. Late deaths in 3 patients were from causes unrelated to pulmonary embolism, and from a further massive pulmonary embolus a week later. The technique has been applied with equal success in a major hospital fully equipped for cardiac surgery and in hospitals where resident and nursing staff had no experience of either thoracic or cardiac surgery. The simplicity and speed of the method has enabled the obstructed right ventricle to be relieved within thirty minutes of the onset of symptoms. The interval between induction of anaesthesia and the skin incision should be kept as short as possible, and drugs to maintain the blood pressure should be given. The period between skin incision and the restoration of the circulation has, with practice, been reduced to ten minutes.

But this clearly still requires surgical expertise and facilities. Emergency physicians can open the chest to deal with penetrating trauma. Could an ED thoracotomy facilitate clot removal from the pulmonary artery?

In 1969, a lady in her 50s arrested on the ward after an operation to remove a mass via a left lateral thoractomy. Pulmonary embolism was suspected and her thoracotomy wound was re-opened and the pulmonary artery incised, resulting in the removal of large amounts of clot. Return of spontaneous circulation resulted after a brief period of internal cardiac massage. Her case was written up decades later, in 1998(3):

The patient recovered rapidly and left the hospital on the 21st day without signs of cerebral damage. This patient is now 86 years old, mentally normal, living alone, and doing her own housekeeping. She remembers the hospital stay and the past years as worth living

Some patients may be considered too high risk for surgery and in some centres Extracorporeal Membrane Oxygenation (ECMO) is an option. It has been used both as life support pending surgery(4), or as an alternative to surgery to allow heparinisation to be used(5,6).

In summary, some patients with massive pulmonary embolism may benefit from surgery (contraindication to ‘lysis or failed ‘lysis). Getting them to surgery alive, or operating on them during cardiac arrest, is a challenge. Ideally they would undergo embolectomy under cardopulmonary bypass in the operating room, or could be placed on ECMO in the ED prior to going to the OR. If they present to a centre without these facilities, then the venous inflow occlusion technique could be used in the OR without bypass. Just rarely a patient may present in extremis with PE to an ED without these options. If that patient has major contraindications to thrombolysis, would an ED thoracotomy be something you would entertain?

I have done several thoracotomies for penetrating trauma but never for PE. I do not pretend to know how, and cannot find a case report of ED thoracotomy for pulmonary embolism in the literature. I’m therefore NOT recommending it. However, I would love to know people’s views on its feasibility. A possible approach could be summarised as:

Massive pulmonary embolism fascinates me, because it’s seen in the ‘talk and die’ patient. It is a single, treatable pathology that if diagnosed and treated appropriately truly makes the difference between life and death. When medicine presents us with an opportunity ‘on a plate’ like that to save a life, we need to be prepared. I have had great saves with this diagnosis and sadly have seen disastrous failures to act. When the time comes, we need to ask: ‘have we explored all options?’.

1. Surgical treatment of acute pulmonary embolism–a 12-year retrospective analysis.
Scand Cardiovasc J. 2012 Jun;46(3):172-6. Epub 2012 Mar 27.

OBJECTIVES: Surgical embolectomy for acute pulmonary embolism (PE) is considered to be a high risk procedure and therefore a last treatment option. We wanted to evaluate the procedures role in modern treatment of acute PE.
DESIGN: All data on patients treated with surgical embolectomy for acute PE were retrieved from our clinical database. The mortality was extracted from the Danish mortality register.
RESULTS: From October 1998 to July 2010, 33 patients underwent surgical embolectomy. All procedures were done through a median sternotomy and extracorporeal circulation. Twenty-six patients were diagnosed with a high risk PE and 7 with an intermediate risk PE and intracardial pathology. Six patients had been insufficiently treated with thrombolysis. Thirteen patients had contraindication for thrombolysis. Six patients were brought to the operating theatre in cardiogenic shock, 8 needed ventilator support, and 1 was in cardiac arrest. The postoperative 30-day mortality was 6% and during the 12-year follow-up the cumulative survival was 80% with 4 late deaths.
CONCLUSION: Surgical pulmonary embolectomy can be performed with low mortality although the treated patients belong to the most compromised part of the PE population. The results support surgical embolectomy as a vital part of the treatment algorithm for acute PE.

2. Pulmonary embolectomy with venous inflow-occlusion.
The Lancet 1972;1(7754):767–769

Massive pulmonary emboli have been removed surgically from 26 patients. The technique of normothermic circulatory arrest by venous inflow-occlusion was used in 25 patients. 13 patients survived. There were 10 operative deaths and 3 hospital deaths. Diagnosis was based upon clinical findings supplemented by electrocardiography and a plain radiograph of the chest. Surgery was offered to patients having a pulmonary embolus sufficiently massive to produce sustained hypotension. All patients whose hearts stopped beating before the embolectomy died. 6 successful operations were performed in hospitals without facilities for cardiac surgery. The method is recommended for its simplicity.

3. Left Anterior Thoracotomy for Pulmonary Embolectomy With 29-Year Follow-up
The Annals of Thoracic Surgery 1998, 66(4):1420-1421

Pulmonary embolectomy is usually performed in cardiopulmonary bypass. In acute situations too much time can be lost in setting up and connecting the pump oxygenator; this delay can cause cerebral damage in a patient with circulatory arrest. In such a situation left anterior thoracotomy can provide an ideal approach. An emergency thoracotomy can be performed in a few seconds. The lung automatically retracts. The phrenic nerve, pulmonary artery, and pericardium are clearly seen, and they outline the area for embolectomy. A case in which such an approach was successfully used is described.

4.ECMO treatment saved life of a young woman with acute pulmonary embolism
Lakartidningen 2004, 101(44):3420-3421

A 42-year old obese female using contraceptive medication was admitted to the emergency room because of sudden onset of dyspnoea and hypoxia. Computed tomography showed massive pulmonary emboli. Despite initial treatment with thrombolysis her condition deteriorated further and she was referred for acute surgery to our clinic. Before putting the patient to sleep extracorporeal circulation was instituted with access from the groin. After anaesthesia a median sternotomy was performed. With the heart beating, the main pulmonary artery was incised and a 9 cm long thrombus was removed. Immediate weaning from the heart-lung machine was not possible, mainly because of bleeding to the airways. The right atrium and the aorta was therefore cannulated and an extracorporeal circulation membrane oxygenator (ECMO) was used for three days. The patient required several re-entries for bleeding and a tracheotomy during the postoperative course. She was fully recovered three months after the operation.

5. Extracorporeal membrane oxygenator for pulmonary embolism.
The Annals of Thoracic Surgery 1997, 64(3):883-884 Free full text

6. Peripheral Extracorporeal Membrane Oxygenation: Comprehensive Therapy for High-Risk Massive Pulmonary Embolism
Ann Thorac Surg 2012;94:104–8

Background: Although commonly reserved as a last line of defense, experienced centers have reported excellent results with pulmonary embolectomy for massive and submassive pulmonary embolism (PE). We present a contemporary surgical series for PE that demonstrates the utility of peripheral extracorporeal membrane oxygenation (pECMO) for high-risk surgical candidates.
Methods: Between June 2005 and April 2011, 29 patients were treated for massive or submassive pulmonary embolism, with surgical embolectomy performed in 26. Four high-risk patients were placed on pECMO, established by percutaneously cannulating the right atrium through a femoral vein and perfusing by a Dacron graft anastomosed to the axillary artery. A small, extracorporeal, rotary assist device was used, interposing a compact oxygenator in the circuit, and maintaining anticoagulation with heparin.
Results: Extracorporeal membrane oxygenation was weaned in 3 of 4 patients after 5.3 days (5, 5, and 6), with normalization of right ventricular dysfunction and pulmonary artery pressure (44.0 ± 2.0 to 24.5 ± 5.5 mm Hg) by ECHO. Follow-up computed tomographies showed several peripheral, nearly resorbed emboli in 1 case and complete resolution in 2 others. The fourth patient, not improving after 10 days, underwent surgery where an embolic liposarcoma was extracted. For all 29 cases, hospital and 30-day mortality was 0% and all patients were discharged, with average postoperative length of stay of 15 days for embolectomy and 17 days for pECMO.
Conclusions: Heparin therapy with pECMO support is a rapid, effective option for patients who might benefit from pulmonary embolectomy but are at high risk for surgery.