Category Archives: ICU

Stuff relevant to patients on ICU

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

Externally rotate leg for femoral vein access

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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

Acute Med, All Updates, ICU, Resus

Hyperglycaemia & mortality in sepsis – lactate dependent?

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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
[EXPAND Click for abstract]


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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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

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Aeromedical retrieval: invasive vs noninvasive blood pressure

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The chaps from the Emergency Medical Retrieval Service in the UK compared invasive (IABP) and non-invasive blood pressure (NIBP) measurements on the ground and in the air. They concluded that NIBP was unreliable, although it was no worse in the aeromedical environment than in the hospital. Not surprisingly there was a better correlation between the mean IABP and NIBP than systolic or diastolic pressures (oscillometric NIBP devices measure the mean BP and derive systolic and diastolic using an algorithm specific to the device).
In their summary, they recommend:

  • IABP monitoring should be used in any unwell patient in whom accurate blood pressure measurement is desirable.
  • The aeromedical transport environment does not lead to less precise NIBP results than the non-transport environment.
  • Where NIBP measurement is the only option, the mean blood pressure should be used in preference to systolic measurements


Blood pressure measurement is an essential physiological measurement for all critically ill patients. Previous work has shown that non-invasive blood pressure is not an accurate reflection of invasive blood pressure measurement. In a transport environment, the effects of motion and vibration may make non-invasive blood pressure less accurate.

Consecutive critically ill patients transported by a dedicated aeromedical retrieval and critical care transfer service with simultaneous invasive and non-invasive blood pressure measurements were analysed. Two sets of measurements were recorded, first in a hospital environment before departure (pre-flight) and a second during aeromedical transport (in-flight).

A total of 56 complete sets of data were analysed. Bland-Altman plots showed limits of agreement (precision) for pre-flight systolic blood pressure were -37.3 mmHg to 30.0 mmHg, and for pre-flight mean arterial pressure -20.5 mmHg to 25.0 mmHg. The limits of agreement for in-flight systolic blood pressure were -40.6 mmHg to 33.1 mmHg, while those for in-flight mean blood pressure in-flight were -23.6 mmHg to 24.6 mmHg. The bias for the four conditions ranged from 0.5 to -3.8 mmHg. There were no significant differences in values between pre-flight and in-flight blood pressure measurements for all categories of blood pressure measurement.

Thus, our data show that non-invasive blood pressure is not a precise reflection of invasive intra-arterial blood pressure. Mean blood pressure measured non-invasively may be a better marker of invasive blood pressure than systolic blood pressure. Our data show no evidence of non-invasive blood pressures being less accurate in an aeromedical transport environment.

Comparison of non-invasive and invasive blood pressure in aeromedical care
Anaesthesia. 2012 Dec;67(12):1343-7

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, Guidelines, ICU, PHARM, Resus, Trauma

A whole bunch of trauma guidelines

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The Eastern Association for the Surgery of Trauma has published a number of helpful evidence-based guidelines for trauma management, and many of them are included in this month’s Journal of Trauma and Acute Care Surgery
Here are brief snippets from some of them. All the guidelines can be viewed or downloaded in full for free here.
 
Nonoperative management of blunt hepatic injury

  • Nonoperative management of blunt hepatic injuries currently is the treatment modality of choice in hemodynamically stable patients, irrespective of the grade of injury or patient age.
  • Patients presenting with hemodynamic instability and peritonitis still warrant emergent operative intervention.
  • Intravenous contrast enhanced computed tomographic scan is the diagnostic modality of choice for evaluating blunt hepatic injuries.

 
Selective nonoperative management of blunt splenic injury

  • Nonoperative management of blunt splenic injuries is now the treatment modality of choice in hemodynamically stable patients, irrespective of the grade of injury, patient age, or the presence of associated injuries.
  • Patients presenting with hemodynamic instability and peritonitis still warrant emergent operative intervention.
  • Intravenous contrast enhanced computed tomographic scan is the diagnostic modality of choice for evaluating blunt splenic injuries.

 
Screening for blunt cardiac injury

  • Electrocardiogram (ECG) alone is not sufficient to rule out BCI.
  • BCI can be ruled out only if both ECG result and troponin I level are normal, a significant change from the previous guideline.
  • Patients with new ECG changes and/or elevated troponin I should be admitted for monitoring.
  • Echocardiogram is not beneficial as a screening tool for BCI and should be reserved for patients with hypotension and/or arrhythmias.
  • The presence of a sternal fracture alone does not predict BCI.
  • Cardiac computed tomography or magnetic resonance imaging can be used to differentiate acute myocardial infarction from BCI in trauma patients.

 
Evaluation and management of penetrating lower extremity arterial trauma

  • Expedited triage of patients is possible with physical examination and/or the measurement of ankle-brachial indices.
  • Computed tomographic angiography has become the diagnostic study of choice when imaging is required.
  • Tourniquets and intravascular shunts have emerged as adjuncts in the treatment of penetrating lower extremity arterial trauma.

 
Prophylactic antibiotic use in penetrating abdominal trauma

  • There is evidence to support a Level I recommendation that prophylactic antibiotics should only be administered for 24 hours in the presence of a hollow viscus injury.
  • There are no data to support continuing prophylactic antibiotics longer than 24 hours in damage control laparotomy.

 
Screening for thoracolumbar spinal injuries in blunt trauma

  • Multidetector computed tomographic scans have become the screening modality of choice and the criterion standard in screening for TLS injuries.
  • Patients without altered mentation or significant mechanism may be excluded by clinical examination without imaging.
  • Patients with gross neurologic deficits or concerning clinical examination findings with negative imaging should receive a magnetic resonance imaging expediently, and the spine service should be consulted

 
Emergency tracheal intubation immediately following traumatic injury

  • The decision to intubate a patient following traumatic injury is based on multiple factors, including the need for oxygenation and ventilation, the extent and mechanism of injury, predicted operative need, or progression of disease.
  • Rapid sequence intubation with direct laryngoscopy continues to be the recommended method for ETI, although the use of airway adjuncts such as blind insertion supraglottic devices and video laryngoscopy may be useful in facilitating successful ETI and may be preferred in certain patient populations.
  • There is no pharmacologic induction agent of choice for ETI; however, succinylcholine is the neuromuscular blockade agent recommended for rapid sequence intubation.

 
Presumptive antibiotic use in tube thoracostomy for traumatic hemopneumothorax

  • Routine presumptive antibiotic use to reduce the incidence of empyema and pneumonia in TT for traumatic hemopneumothorax is controversial; however, there is insufficient published evidence to support any recommendation either for or against this practice.

 
Evaluation and management of geriatric trauma

  • Effective evidence-based care of aging patients necessitates aggressive triage, correction of coagulopathy, and limitation of care when clinical evidence points toward an overwhelming likelihood of poor long-term prognosis

 
Management of pulmonary contusion and flail chest

  • Patients with PC-FC should not be excessively fluid restricted but should be resuscitated to maintain signs of adequate tissue perfusion.
  • Obligatory mechanical ventilation in the absence of respiratory failure should be avoided.
  • The use of optimal analgesia and aggressive chest physiotherapy should be applied to minimize the likelihood of respiratory failure.
  • Epidural catheter is the preferred mode of analgesia delivery in severe flail chest injury.
  • Paravertebral analgesia may be equivalent to epidural analgesia and may be appropriate in certain situations when epidural is contraindicated.
  • A trial of mask continuous positive airway pressure should be considered in alert patients with marginal respiratory status.
  • Patients requiring mechanical ventilation should be supported in a manner based on institutional and physician preference and separated from the ventilator at the earliest possible time.
  • Positive end-expiratory pressure or continuous positive airway pressure should be provided.
  • High-frequency oscillatory ventilation should be considered for patients failing conventional ventilatory modes. Independent lung ventilation may also be considered in severe unilateral pulmonary contusion when shunt cannot be otherwise corrected.
  • Surgical fixation of flail chest may be considered in cases of severe flail chest failing to wean from the ventilator or when thoracotomy is required for other reasons.
  • Self-activating multidisciplinary protocols for the treatment of chest wall injuries may improve outcome and should be considered where feasible.
  • Steroids should not be used in the therapy of pulmonary contusion.
  • Diuretics may be used in the setting of hydrostatic fluid overload in hemodynamically stable patients or in the setting of known concurrent congestive heart failure.

 
Evaluation and management of small-bowel obstruction

  • Level I evidence now exists to recommend the use of computed tomographic scan, especially multidetector computed tomography with multiplanar reconstructions, in the evaluation of patients with SBO because it can provide incremental clinically relevant information over plains films that may lead to changes in management.
  • Patients with evidence of generalized peritonitis, other evidence of clinical deterioration, such as fever, leukocytosis, tachycardia, metabolic acidosis, and continuous pain, or patients with evidence of ischemia on imaging should undergo timely exploration.
  • The remainder of patients can safely undergo initial nonoperative management for both partial and complete SBO.
  • Water-soluble contrast studies should be considered in patients who do not clinically resolve after 48 to 72 hours for both diagnostic and potential therapeutic purposes.
  • Laparoscopic treatment of SBO has been demonstrated to be a viable alternative to laparotomy in selected cases.

 
2012 Eastern Association for the Surgery of Trauma (EAST) Practice Management Guidelines Supplement
J Trauma Acute Care Surg. 2012 Nov;73(5 Suppl 4)

All Updates, ICU, PHARM, Resus, Trauma

Needle decompression: it's still not going to work

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A pet topic that keeps coming up here is management of tension pneumothorax. Plenty of studies demonstrate that traditionally taught needle thoracostomy may fail, and open, or ‘finger’ thoracostomy is recommended for the emergency management of tension pneumothorax in a patient who is being ventilated with positive pressure (including those patients in cardiac arrest).
A recent CT scan-based study of adult trauma patients makes the case that needle decompression with a standard iv cannula would be expected to fail in 42.5% of cases at the second intercostal space (ICS) compared with 16.7% at the fifth ICS at the anterior axillary line (AAL).
The authors add an important point: “As BMI increases, there is a stepwise increase in chest wall thickness, further compounding the difficulty of needle placement in all but the lowest BMI quartile for the second ICS.”
An accompanying editorial cautions that the proximity of the heart may confer a safety issue if a needle is inserted blindly into the left 5th ICS at the AAL.


Objective To compare the distance to be traversed during needle thoracostomy decompression performed at the second intercostal space (ICS) in the midclavicular line (MCL) with the fifth ICS in the anterior axillary line (AAL).

Design Patients were separated into body mass index (BMI) quartiles, with BMI calculated as weight in kilograms divided by height in meters squared. From each BMI quartile, 30 patients were randomly chosen for inclusion in the study on the basis of a priori power analysis (n = 120). Chest wall thickness on computed tomography at the second ICS in the MCL was compared with the fifth ICS in the AAL on both the right and left sides through all BMI quartiles.

Setting Level I trauma center.

Patients Injured patients aged 16 years or older evaluated from January 1, 2009, to January 1, 2010, undergoing computed tomography of the chest.

Results A total of 680 patients met the study inclusion criteria (81.5% were male and mean age was 41 years [range, 16-97 years]). Of the injuries sustained, 13.2% were penetrating, mean (SD) Injury Severity Score was 15.5 (10.3), and mean BMI was 27.9 (5.9) (range, 15.4-60.7). The mean difference in chest wall thickness between the second ICS at the MCL and the fifth ICS at the AAL was 12.9 mm (95% CI, 11.0-14.8; P < .001) on the right and 13.4 mm (95% CI, 11.4-15.3; P < .001) on the left. There was a stepwise increase in chest wall thickness across all BMI quartiles at each location of measurement. There was a significant difference in chest wall thickness between the second ICS at the MCL and the fifth ICS at the AAL in all quartiles on both the right and the left. The percentage of patients with chest wall thickness greater than the standard 5-cm decompression needle was 42.5% at the second ICS in the MCL and only 16.7% at the fifth ICS in the AAL.

Conclusions In this computed tomography–based analysis of chest wall thickness, needle thoracostomy decompression would be expected to fail in 42.5% of cases at the second ICS in the MCL compared with 16.7% at the fifth ICS in the AAL. The chest wall thickness at the fifth ICS AAL was 1.3 cm thinner on average and may be a preferred location for needle thoracostomy decompression.

Radiologic evaluation of alternative sites for needle decompression of tension pneumothorax
Arch Surg. 2012 Sep 1;147(9):813-8

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

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Don't bronchodilators work in infants?

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Inpatient paediatric teams can be scornful when bronchodilators are given by ED staff to wheezing infants, correctly referring to the lack of evidence of clinical benefit(1). There is however a persisting meme out there I’ve heard on a number of occasions that ‘young infants don’t have the receptors so inhaled beta agonists will never work.’ I’d love to know where this comes from.
Apparently, beta 2-receptors are present from the 16th gestational week(2). Pulmonary function testing of ventilated, very-low-birth-weight babies has shown that some consistently responded to beta-agonists whereas others did not(3). A newly published study reports that a quarter of mechanically ventilated infants with bronchiolitis were responders to inhaled albuterol, defined as a reduction in respiratory system resistance more than 30% below baseline(4).
In summary: beta-agonist bronchodilators have not been shown to improve clinical outcomes in wheezing infants. However some infants with some wheezing disorders will show a response in terms of pulmonary function. The receptors are there, and in life-threatening presentations bronchodilators should certainly be considered.
1. Short acting beta agonists for recurrent wheeze in children under 2 years of age
Cochrane Database Syst Rev. 2002;(3):CD002873
[EXPAND Click to read abstract]


BACKGROUND: Wheeze is a common symptom in infancy and is a common cause for both primary care consultations and hospital admission. Beta2-adrenoceptor agonists (b2-agonists) are the most frequently used as bronchodilator but their efficacy is questionable.
OBJECTIVES: To determine the effectiveness of b2-agonist for the treatment of infants with recurrent and persistent wheeze.
SEARCH STRATEGY: Relevant trials were identified using the Cochrane Airways Group database (CENTRAL), Medline and Pubmed. The database search used the following terms: Wheeze or asthma and Infant or Child and Short acting beta-agonist or Salbutamol (variants), Albuterol, Terbutaline (variants), Orciprenaline, Fenoterol

SELECTION CRITERIA: Randomised controlled trials comparing the effect of b2-agonist against placebo in children under 2 years of age who had had two or more previous episodes of wheeze, not related to another form of chronic lung disease.
DATA COLLECTION AND ANALYSIS: Eight studies met the criteria for inclusion in this meta-analysis. The studies investigated patients in three settings: at home (3 studies), in hospital (2 studies) and in the pulmonary function laboratory (3 studies). The main outcome measure was change in respiratory rate except for community based studies where symptom scores were used.

MAIN RESULTS: The studies were markedly heterogeneous and between study comparisons were limited. Improvement in respiratory rate, symptom score and oxygen saturation were noted in one study in the emergency department following two salbutamol nebulisers but this had no impact on hospital admission. There was a reduction in bronchial reactivity following salbutamol. There was no significant benefit from taking regular inhaled salbutamol on symptom scores recorded at home.

REVIEWER’S CONCLUSIONS: There is no clear benefit of using b2-agonists in the management of recurrent wheeze in the first two years of life although there is conflicting evidence. At present, further studies should only be performed if the patient group can be clearly defined and there is a suitable outcome parameter capable of measuring a response.

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2. The beta-2-agonists in asthma in infants and young children
Arch Pediatr. 2002 Aug;9 Suppl 3:384s-389s
[EXPAND Click to read abstract]


Beta 2-agonists, by inducing a fast and long relaxation of the bronchial smooth muscle, are considered as the more potent bronchodilators. beta 2-receptors are present from the 16th gestational week, explaining a possible bronchial response in the youngest children. beta 2-agonists do not induce any bronchodilator response in healthy children. Short-acting beta 2-agonists (salbutamol or albuterol, terbutaline) are indicated for asthma attacks, as needed in chronic asthma, and for prevention of symptoms during effort. They are safe and secure. The more efficient route of administration in preschool children is pressurized metered-dose inhaler used with a spacer device. Therefore, whatever the route of inhalation chosen (inhalation, injection, or continuous nebulization in acute asthma attack), more specified indications and doses are needed in young children. Long-acting beta 2-agonists (formoterol, salmeterol) are not authorized in France in children under 4 to 5 years of age depending on the drug used. Because of new oral formulations and recent considerations about their use in asthma attack, instead of short-acting beta 2-agonists, their indication in preschool asthmatic children might be reconsidered.

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3. Use of a beta-agonist in ventilated, very-low-birth-weight babies: a longitudinal evaluation
Dev Pharmacol Ther. 1990;15(2):61-7
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To determine if there is a specific postnatal (PNA) or postconceptional age (PCA) at which ventilated preterm infants respond to beta-agonists, we evaluated 15 infants with a mean gestational age of 26.5 +/- 1.5 weeks and mean birth weight of 0.89 +/- 0.23 kg who required mechanical ventilation at 10 days of age. Weekly pulmonary function testing (PFT) was performed before and 1 h after administration of albuterol. Taking the group as a whole, as well as individual babies, regression analysis showed no relationship between positive response and either PNA or PCA. Evaluation of individual infants, however, showed that some consistently responded to beta-agonists whereas others did not. We recommend individual PFT to identify those infants who will benefit from use of beta-agonists.

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4. Pulmonary mechanics following albuterol therapy in mechanically ventilated infants with bronchiolitis
J Asthma. 2012 Sep;49(7):688-96
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BACKGROUND AND AIMS: Bronchiolitis is a common cause of critical illness in infants. Inhaled β(2)-agonist bronchodilators are frequently used as part of treatment, despite unproven effectiveness. The purpose of this study was to describe the physiologic response to these medications in infants intubated and mechanically ventilated for bronchiolitis.

MATERIALS AND METHODS: We conducted a prospective trial of albuterol treatment in infants intubated and mechanically ventilated for bronchiolitis. Before and for 30 minutes following inhaled albuterol treatment, sequential assessments of pulmonary mechanics were determined using the interrupter technique on repeated consecutive breaths.

RESULTS: Fifty-four infants were enrolled. The median age was 44 days (25-75%; interquartile range (IQR) 29-74 days), mean hospital length of stay (LOS) was 18.3 ± 13.3 days, mean ICU LOS was 11.3 ± 6.4 days, and mean duration of mechanical ventilation was 8.5 ± 3.5 days. Fifty percent (n = 27) of the infants were male, 81% (n = 44) had public insurance, 80% (n = 41) were Caucasian, and 39% (n = 21) were Hispanic. Fourteen of the 54 (26%) had reduction in respiratory system resistance (Rrs) that was more than 30% below baseline, and were defined as responders to albuterol. Response to albuterol was not associated with demographic factors or hospitalization outcomes such as LOS or duration of mechanical ventilation. However, increased Rrs, prematurity, and non-Hispanic ethnicity were associated with increased LOS.

CONCLUSIONS: In this population of mechanically ventilated infants with bronchiolitis, relatively few had a reduction in pulmonary resistance in response to inhaled albuterol therapy. This response was not associated with improvements in outcomes.

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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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