Category Archives: Acute Med

Acute care of the medically sick adult

Acute Med, All Updates, PHARM

Enoxaparin beats heparin for PCI

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This is of interest to those of us in retrieval medicine, for logistic reasons: an infusion of heparin can be an unnecessary hassle during transport, especially if a subcutaneous injection prior to retrieval is a satisfactory alternative. This systematic review and meta-analysis shows enoxaparin appears to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention. This applies particularly to patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction


OBJECTIVE: To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline and Cochrane database of systematic reviews, January 1996 to May 2011.

STUDY SELECTION: Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes.

DATA EXTRACTION: Sample size, characteristics, and outcomes, extracted independently and analysed.

DATA SYNTHESIS: 23 trials representing 30 966 patients were identified, including 10 243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11 973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13 943 patients (45.0%) received enoxaparin and 17 023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01).
CONCLUSION: Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction.

Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis
BMJ. 2012 Feb 3;344:e553

Acute Med, All Updates, ICU, Resus, Ultrasound

Posterior pericardiocentesis

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Dr Emanuele Catena and colleagues report a case of an adult male who presented 7 days post cardiac surgery with simultaneous pleural and pericardial effucions causing dyspnoea, tachycardia and hypotension.

Old skool pericardiocentesis

His pericardial effusion was posterior which usually requires surgical drainage, but the adjacent left pleural effusion was associated with pulmonary atelectasis and displacement of the lung, allowing them to insert a needle using sonographic guidance first into the pleural space then the pericardial space.
They inserted through the fourth intercostal space 4 cm medially to the left posterior axillary line (with the patient positioned in the semireclining position). They used agitated saline bubbles to confirm first the pleural then the pericardial location of the needle tip. A 30-cm-long catheter was introduced into the posterior pericardium using the Seldinger technique, and serous-haemorrhagic fluid was drained. The catheter was then retracted allowing drainage of the pleural effusion.
The procedure resulted in haemodynamic and respiratory improvement.
The authors summarise:


This case reports the technique of a “back pericardiocentesis” performed under echographic guidance as a valid alternative to surgery in the peculiar situation characterized by the simultaneous presence of a large left pleural effusion. In the presence of a large left pleural effusion, pulmonary atelectasis and displacement of air-filled pulmonary tissue allows ultrasound transmission from a patient’s back to the heart through a liquid interface and needle insertion “from back” to reach the pericardial space.

 
Pericardiocentesis From Back Under Echographic Guidance An Approach for Posterior Pericardial Effusions
Circulation. 2011 Dec 13;124(24):e835-6

Acute Med, All Updates, PHARM, Resus, Ultrasound

Prehospital echo predicts arrest outcome

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In hospital, the detection of cardiac standstill with ultrasound predicts a fatal outcome from cardiac arrest with a high degree of accuracy. A similar finding has been made in the prehospital setting. Interestingly, it was a better predictor than other commonly recognised factors associated with outcome: the presence of asystole, down time, bystander CPR, or end-tidal CO2 levels.


Introduction. The prognostic value of emergency echocardiography (EE) in the management of cardiac arrest patients has previously been studied in an in-hospital setting. These studies mainly included patients who underwent cardiopulmonary resuscitation (CPR) by emergency medicine technicians at the scene and who arrived at the emergency department (ED) still in a state of cardiac arrest. In most European countries, cardiac arrest patients are normally treated by physician-staffed emergency medical services (EMS) teams on scene. Transportation to the ED while undergoing CPR is uncommon. Objective. To evaluate the ability of EE to predict outcome in cardiac arrest patients when it is performed by ultrasound-inexperienced emergency physicians on scene.

Methods. We performed a prospective, observational study of nonconsecutive, nontrauma, adult cardiac arrest patients who were treated by physician-staffed urban EMS teams on scene. Participating emergency physicians (EPs) received a two-hour course in EE during CPR. After initial procedures were accomplished, EE was performed during a rhythm and pulse check. A single subxiphoid, four-chamber view was required for study enrollment. We defined sonographic evidence of cardiac kinetic activity as any detected motion of the myocardium, ranging from visible ventricular fibrillation to coordinated ventricular contractions. The CPR had to be continued for at least 15 minutes after the initial echocardiography. No clinical decisions were made based on the results of EE.

Results. Forty-two patients were enrolled in the study. The heart could be visualized successfully in all patients. Five (11.9%) patients survived to hospital admission. Of the 32 patients who had cardiac standstill on initial EE, only one (3.1%) survived to hospital admission, whereas four out of 10 (40%) patients with cardiac movement on initial EE survived to hospital admission (p = 0.008). Neither asystole on initial electrocardiogram nor peak capnography value, age, bystander CPR, or downtime was a significant predictor of survival. Only cardiac movement was associated with survival, and cardiac standstill at any time during CPR resulted in a positive predictive value of 97.1% for death at the scene.

Conclusion. Our results support the idea of focused echocardiography as an additional criterion in the evaluation of outcome in CPR patients and demonstrate its feasibility in the prehospital setting.

Cardiac Movement Identified on Prehospital Echocardiography Predicts Outcome
Prehosp Emerg Care. 2012 Jan 11. [Epub ahead of print]

Acute Med, All Updates, ICU, Resus

β-2 agonists could worsen ARDS outcome

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Image: Wikipedia. I really fancy a curry now.

A previous study (BALTI-1) suggested β-2 agonists may help in ARDS by reducing extravascular lung water. A randomised trial in the UK aimed to recruit 1334 patients to compare intravenous salbutamol infused for seven days with placebo (0.9% saline). However the Data Monitoring and Ethics Committee recommended that the study stop after the second interim analysis of 273 patients because of a significant increase in mortality. It is unclear why salbutamol is harmful, and could be due to lung, cardiovascular, or other metabolic effects, such as activation of the renin-angiotensin aldosterone system affecting fluid balance.


BACKGROUND:In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS.

METHODS:We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minimisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FiO2) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86.

FINDINGS:We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03-2·08).

INTERPRETATION:Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended.

FUNDING:UK Medical Research Council, UK Department of Health, UK Intensive Care Foundation.

Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial
Lancet 379(9812, 21–27 January 2012, Pages 229–235

Acute Med, All Updates, ICU, Resus

Vasopressin – what it does and doesn't do

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The current Surviving Sepsis campaign guidelines recommend that vasopressin should not be administered as the initial vasopressor in septic shock, and that vasopressin at constant dosage of 0.03 units/min may be added to norepinephrine with anticipation of an effect equivalent to that of norepinephrine alone. European intensivists conducted a systematic review to determine vasopressin’s risks and benefits in vasodilatory shock. There was no demonstrated survival benefit but its use is associated with a significant reduction in norepinephrine requirement.
Interestingly, the authors point out: ‘Low-dose vasopressin may help to restore blood pressure in patients with hypotension refractory to catecholamines, and may favor pulmonary vasodilation and increase glomerular filtration rate and plasma cortisol levels’.
My take home: consider its use if an apparent vasodilatory shock state is refractory to catecholamines, but don’t stress if you don’t have access to it (or it will complicate practical aspects of organising resuscitation and transfer), since there’s still no clear evidence for outcome benefit.


OBJECTIVE:
To examine the benefits and risks of vasopressin or its analog terlipressin for patients with vasodilatory shock.

DATA SOURCE:
We searched the CENTRAL, MEDLINE, EMBASE, and LILACS databases (up to March 2011) as well as reference lists of articles and proceedings of major meetings; we also contacted trial authors. We considered randomized and quasirandomized trials of vasopressin or terlipressin versus placebo or supportive treatment in adult and pediatric patients with vasodilatory shock. The primary outcome for this review was short-term all-cause mortality.

STUDY SELECTION:
We identified 10 randomized trials (1,134 patients). Six studies were considered for the main analysis on mortality in adults.

DATA EXTRACTION AND SYNTHESIS:
The crude short-term mortality was 206 of 512 (40.2%) in vasopressin/terlipressin-treated patients and 198 of 461 (42.9%) in controls [six trials, risk ratio (RR) = 0.91; 95% confidence interval (CI) 0.79-1.05; P = 0.21; I (2) = 0%]. There were 49 of 463 (10.6%) patients with serious adverse events in the vasopressin/terlipressin arm and 51 of 431 (11.8%) in the control arm (four trials, RR = 0.90; 95% CI 0.49-1.67; P = 0.75; I (2) = 26%). Metaregression analysis showed negative correlation between vasopressin dose and norepinephrine dose (P = 0.03).

CONCLUSIONS:
Overall, use of vasopressin or terlipressin did not produce any survival benefit in the short term in patients with vasodilatory shock. Physicians may value the sparing effects of vasopressin/terlipressin on norepinephrine requirement given its apparent safe profile.

Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis
Intensive Care Med. 2012 Jan;38(1):9-19

Acute Med, All Updates, ICU, Resus, Ultrasound

Ultrasound for pneumonia

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Lung ultrasound done by a single keen individual had better test characteristics than CXR in diagnosing pneumonia as defined by discharge diagnosis.
The lung ultrasound was considered to be positive for pneumonia if it showed consolidation (including air bronchograms) or a focal interstitial syndrome (localised increased density of ‘B’ lines)


Objective The aim of this study was to evaluate the diagnostic accuracy of bedside lung ultrasound and chest radiography (CXR) in patients with suspected pneumonia compared with CT scan and final diagnosis at discharge.

Design A prospective clinical study.

Methods Lung ultrasound and CXR were performed in sequence in adult patients admitted to the emergency department (ED) for suspected pneumonia. A chest CT scan was performed during hospital stay when clinically indicated.

Results 120 patients entered the study. A discharge diagnosis of pneumonia was confirmed in 81 (67.5%). The first CXR was positive in 54/81 patients (sensitivity 67%; 95% CI 56.4% to 76.9%) and negative in 33/39 (specificity 85%; 95% CI 73.3% to 95.9%), whereas lung ultrasound was positive in 80/81 (sensitivity 98%; 95% CI 93.3% to 99.9%) and negative in 37/39 (specificity 95%; 95% CI 82.7% to 99.4%). A CT scan was performed in 30 patients (26 of which were positive for pneumonia); in this subgroup the first CXR was diagnostic for pneumonia in 18/26 cases (sensitivity 69%), whereas ultrasound was positive in 25/26 (sensitivity 96%). The feasibility of ultrasound was 100% and the examination was always performed in less than 5 min.

Conclusions Bedside chest ultrasound is a reliable tool for the diagnosis of pneumonia in the ED, probably being superior to CXR in this setting. It is likely that its wider use will allow a faster diagnosis, conducive to a more appropriate and timely therapy.

Lung ultrasound is an accurate diagnostic tool for the diagnosis of pneumonia in the emergency department
Emerg Med J. 2012 Jan;29(1):19-23

Acute Med, All Updates, ICU, Resus

Potassium levels and AMI death

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An association is demonstrated between abnormal (both high and low) serum potassium levels and in-hospital mortality in patients with acute myocardial infarction. These findings do not necessarily imply a causal relationship, since abnormal potassium levels might be a marker of increased risk of death due to other illness factors rather than a risk of death per se.
Acknowledging that a randomised trial of potassium replacement is unlikely to happen, the authors pragmatically advise:
Our data suggest that the optimal range of serum potassium levels in AMI patients may be between 3.5 and 4.5 mEq/L and that potassium levels of greater than 4.5 mEq/L are associated with increased mortality and should probably be avoided.


Context Clinical practice guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L in patients with acute myocardial infarction (AMI). These guidelines are based on small studies that associated low potassium levels with ventricular arrhythmias in the pre−β-blocker and prereperfusion era. Current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Objective To determine the relationship between serum potassium levels and in-hospital mortality in AMI patients in the era of β-blocker and reperfusion therapy.

Design, Setting, and Patients Retrospective cohort study using the Cerner Health Facts database, which included 38 689 patients with biomarker-confirmed AMI, admitted to 67 US hospitals between January 1, 2000, and December 31, 2008. All patients had in-hospital serum potassium measurements and were categorized by mean postadmission serum potassium level (<3.0, 3.0-<3.5, 3.5-<4.0, 4.0-<4.5, 4.5-<5.0, 5.0-<5.5, and ≥5.5 mEq/L). Hierarchical logistic regression was used to determine the association between potassium levels and outcomes after adjusting for patient- and hospital-level factors.
Main Outcome Measures All-cause in-hospital mortality and the composite of ventricular fibrillation or cardiac arrest.

Results There was a U-shaped relationship between mean postadmission serum potassium level and in-hospital mortality that persisted after multivariable adjustment. Compared with the reference group of 3.5 to less than 4.0 mEq/L (mortality rate, 4.8%; 95% CI, 4.4%-5.2%), mortality was comparable for mean postadmission potassium of 4.0 to less than 4.5 mEq/L (5.0%; 95% CI, 4.7%-5.3%), multivariable-adjusted odds ratio (OR), 1.19 (95% CI, 1.04-1.36). Mortality was twice as great for potassium of 4.5 to less than 5.0 mEq/L (10.0%; 95% CI, 9.1%-10.9%; multivariable-adjusted OR, 1.99; 95% CI, 1.68-2.36), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. In contrast, rates of ventricular fibrillation or cardiac arrest were higher only among patients with potassium levels of less than 3.0 mEq/L and at levels of 5.0 mEq/L or greater.

Conclusion Among inpatients with AMI, the lowest mortality was observed in those with postadmission serum potassium levels between 3.5 and <4.5 mEq/L compared with those who had higher or lower potassium levels.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction
JAMA Jan 11 2012,307(2):115-213

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

Two new anaphylaxis guidelines

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Many local and national guidelines for the management of anaphylaxis exist, but did you know there was a World Allergy Organization, and it has a very detailed guideline on this important life threatening condition?

Some interesting snippets from the guideline are included here

Anaphylaxis and cardiac disease

  • Anaphylaxis can precipitate acute myocardial infarction in susceptible individuals: in patients with ischemic heart disease, the number and density of cardiac mast cells is increased, including in the atherosclerotic plaques. Mediators released during anaphylaxis contribute to vasoconstriction and coronary artery spasm.
  • Epinephrine is not contraindicated in the treatment of anaphylaxis in patients with known or suspected cardiovascular disease, or in middle-aged or elderly patients without any history of coronary artery disease who are at increased risk of ACS only because of their age. Through its beta-1 adrenergic effects, epinephrine actually increases coronary artery blood flow because of an increase in myocardial contractility and in the duration of diastole relative to systole.
  • Glucagon has noncatecholamine-dependent inotropic and chronotropic cardiac effects, and is sometimes needed in patients taking a beta-adrenergic blocker who have hypotension and bradycardia and who do not respond optimally to epinephrine.
  • Anticholinergic agents are sometimes needed in beta-blocked patients, for example, atropine in those with persistent bradycardia or ipratropium in those with epinephrine-resistant bronchospasm.

How quickly can untreated anaphylaxis kill you?

Studies show median times to cardiorespiratory arrest after exposure to the offending stimulus were 5 minutes after administration of contrast media or drugs, 15 minutes after an insect sting, and 30 minutes after food ingestion.

What about confirming the diagnosis with serum tryptase measurements?

  • Blood samples for measurement of tryptase levels are optimally obtained 15 minutes to 3 hours after symptom onset.
  • Blood samples for measurement of histamine levels are optimally obtained 15–60 minutes after symptom onset. These tests are not specific for anaphylaxis.
  • Increased serum tryptase levels are often found in patients with anaphylaxis from insect stings or injected medications, and in those who are hypotensive
  • However, levels are often within normal limits in patients with anaphylaxis triggered by food and in those who are normotensive
  • Serial measurement of tryptase levels during an anaphylactic episode, and measurement of a baseline level after recovery are reported to be more useful than measurement at only one point in time.
  • Normal levels of either tryptase or histamine do not rule out the clinical diagnosis of anaphylaxis


How does epinephrine help?

  • Epinephrine is life-saving because of its alpha-1 adrenergic vasoconstrictor effects in most body organ systems (skeletal muscle is an important exception) and its ability to prevent and relieve airway obstruction caused by mucosal edema, and to prevent and relieve hypotension and shock.
  • Other relevant properties in anaphylaxis include its beta-1 adrenergic agonist inotropic and chronotropic properties leading to an increase in the force and rate of cardiac contractions, and its beta-2 adrenergic agonist properties such as decreased mediator release, bronchodilation and relief of urticaria
  • Epinephrine in a dose of 0.01 mg/kg of a 1:1,000 (1 mg/mL) solution injected promptly by the intramuscular route is effective and safe in the initial treatment of anaphylaxis. In other anaphylaxis scenarios, this low first-aid dose is unlikely to be effective. For example, if shock is imminent or has already developed, epinephrine needs to be given by slow intravenous infusion, ideally with the dose titrated according to noninvasive continuous cardiac monitoring.

What is the empty ventricle syndrome?

  • Patients with anaphylaxis should not suddenly sit, stand, or be placed in the upright position.
  • Instead, they should be placed on the back with their lower extremities elevated or, if they are experiencing respiratory distress or vomiting, they should be placed in a position of comfort with their lower extremities elevated.
  • This accomplishes 2 therapeutic goals: 1) preservation of fluid in the circulation (the central vascular compartment), an important step in managing distributive shock; and 2) prevention of the empty vena cava/empty ventricle syndrome, which can occur within seconds when patients with anaphylaxis suddenly assume or are placed in an upright position.
  • Patients with this syndrome are at high risk for sudden death. They are unlikely to respond to epinephrine regardless of route of administration, because it does not reach the heart and therefore cannot be circulated throughout the body

Should we give antihistamines, beta 2 agonists, and steroids?

The evidence base for use of these second line medications in the initial management of anaphylaxis, is extrapolated mainly from their use in treatment of other diseases such as urticaria (antihistamines) or acute asthma (beta-2 adrenergic agonists and glucocorticoids). Concerns have been raised that administering one or more second-line medications potentially delays prompt injection of epinephrine, the first-line treatment


Is ‘biphasic anaphylaxis’ a real phenomenon we should be concerned about?

  • Biphasic anaphylaxis occurs when symptoms recur within 1–72 hours (usually within 8–10 hours) after the initial symptoms have resolved, despite no further exposure to the trigger.
  • It occurs in up to 23% of adults and up to 11% of children.
  • After apparent resolution of symptoms, duration of monitoring in a medically supervised setting should be individualized. For example, patients with moderate respiratory or cardiovascular compromise should be monitored for at least 4 hours, and if indicated, for 8–10 hours or longer.
  • Protracted uniphasic anaphylaxis is uncommon, but can last for days.

World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis
World Allergy Organization Journal 2011;4(2):13-37 Full Text
[EXPAND click for abstract]

The illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of December 2010. The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously). The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed.

[/EXPAND]
This month has also seen the publication guidelines from the UK’s National Institute for Health & Clinical Excellence, entitled ‘Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode’
Their guideline summary is as follows:

After a suspected anaphylactic reaction in adults or young people aged 16 years or older, take timed blood samples for mast cell tryptase testing as follows:

  • a sample as soon as possible after emergency treatment has started
  • a second sample ideally within 1–2 hours (but no later than 4 hours) from the onset of symptoms.

After a suspected anaphylactic reaction in children younger than 16 years, consider taking blood samples for mast cell tryptase testing as follows if the cause is thought to be venom-related, drug-related or idiopathic:

  • a sample as soon as possible after emergency treatment has started
  • a second sample ideally within 1–2 hours (but no later than 4 hours) from the onset of symptoms.

Patients who have had emergency treatment for suspected anaphylaxis should be observed for 6–12 hours from the onset of symptoms, depending on their response to emergency treatment
After emergency treatment for suspected anaphylaxis, offer people a referral to a specialist allergy service (age-appropriate where possible) consisting of healthcare professionals with the skills and competencies necessary to accurately investigate, diagnose, monitor and provide ongoing management of, and patient education about, suspected anaphylaxis.
After emergency treatment for suspected anaphylaxis, offer people (or, as appropriate, their parent and/or carer) an appropriate adrenaline injector as an interim measure before the specialist allergy service appointment.
Before discharge a healthcare professional with the appropriate skills and competencies should offer people (or, as appropriate, their parent and/or carer) the following:

  • information about anaphylaxis, including the signs and symptoms of an anaphylactic reaction
  • information about the risk of a biphasic reaction
  • information on what to do if an anaphylactic reaction occurs (use the adrenaline injector and call emergency services)

Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode
CG134 Anaphylaxis: NICE guideline

Acute Med, All Updates, ICU

Enoxaparin in acute medical patients

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A large multinational study challenges the practice of routine thromboprophylaxis for hospitalised acutely ill medical patients. Enoxaparin plus graduated compression stockings did not reduce 30 day mortality compared with stockings alone. There was no significant difference in the rates of major bleeding.


Background Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, an associated reduction in the rate of death from any cause has not been shown.

Methods We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo — both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression — on the rate of death from any cause among hospitalized, acutely ill medical patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. Inclusion criteria were an age of at least 40 years and hospitalization for acute decompensated heart failure, severe systemic infection with at least one risk factor for venous thromboembolism, or active cancer. The primary efficacy outcome was the rate of death from any cause at 30 days after randomization. The primary safety outcome was the rate of major bleeding during and up to 48 hours after the treatment period.

Results A total of 8307 patients were randomly assigned to receive enoxaparin plus elastic stockings with graduated compression (4171 patients) or placebo plus elastic stockings with graduated compression (4136 patients) and were included in the intention-to-treat population. The rate of death from any cause at day 30 was 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (risk ratio, 1.0; 95% confidence interval [CI], 0.8 to 1.2; P=0.83). The rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group (risk ratio, 1.4; 95% CI, 0.7 to 3.1; P=0.35).

Conclusions The use of enoxaparin plus elastic stockings with graduated compression, as compared with elastic stockings with graduated compression alone, was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients. (Funded by Sanofi; LIFENOX ClinicalTrials.gov number, NCT00622648.)

Low-Molecular-Weight Heparin and Mortality in Acutely Ill Medical Patients
N Engl J Med 2011; 365:2463-2472

Acute Med, All Updates, ICU, Kids, Resus

Treating sepsis – have we got it the wrong way round?

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In our understanding of the pathophysiology of sepsis, we often attribute organ damage and death to the excessive host response to infection, including the popular phrase ‘cytokine storm’. This has been nicely described as ‘friendly fire’ by Prof Derek Angus, who points out that this central tenet of sepsis understanding may in some cases be flawed1; it has led to research on drugs that suppress parts of these inflammatory pathways, although none have yet proven effective. An elegant study on patients dying from sepsis showed clear evidence of immunosuppression compared with controls2.

Editorialist Peter Ward3 proposes an area for future research: whether such derangements can be reversed by treatment with agents such as interleukins 7 or 15, which might combat the T-cell depletion state in sepsis.
The authors point out that all the patients included in the study died on ICU, some after a considerable duration of illness, and they emphasise that early deaths from sepsis in previously healthy patients with infections of highly virulent organisms are associated with an extremely exuberant immunoinflammatory response.
1.The Search for Effective Therapy for Sepsis: Back to the Drawing Board?
JAMA December 21, 2011, Vol 306, No. 23, pp 2614-5
2.Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure
JAMA December 21, 2011, Vol 306, No. 23, pp 2594-2605
[EXPAND Abstract]


Context Severe sepsis is typically characterized by initial cytokine-mediated hyperinflammation. Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting.
Objectives To determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression.
Design, Setting, and Participants Rapid postmortem spleen and lung tissue harvest was performed at the bedsides of 40 patients who died in intensive care units (ICUs) of academic medical centers with active severe sepsis to characterize their immune status at the time of death (2009-2011). Control spleens (n = 29) were obtained from patients who were declared brain-dead or had emergent splenectomy due to trauma; control lungs (n = 20) were obtained from transplant donors or from lung cancer resections.
Main Outcome Measures Cytokine secretion assays and immunophenotyping of cell surface receptor-ligand expression profiles were performed to identify potential mechanisms of immune dysfunction. Immunohistochemical staining was performed to evaluate the loss of immune effector cells.
Results The mean ages of patients with sepsis and controls were 71.7 (SD, 15.9) and 52.7 (SD, 15.0) years, respectively. The median number of ICU days for patients with sepsis was 8 (range, 1-195 days), while control patients were in ICUs for 4 or fewer days. The median duration of sepsis was 4 days (range, 1-40 days). Compared with controls, anti-CD3/anti-CD28–stimulated splenocytes from sepsis patients had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5361 (95% CI, 3327-7485) pg/mL vs 418 (95% CI, 98-738) pg/mL; interferon γ, 1374 (95% CI, 550-2197) pg/mL vs 37.5 (95% CI, −5 to 80) pg/mL; interleukin 6, 3691 (95% CI, 2313-5070) vs 365 (95% CI, 87-642) pg/mL; and interleukin 10, 633 (95% CI, −269 to 1534) vs 58 (95% CI, −39 to 156) pg/mL; (P < .001 for all). There were similar reductions in 5-hour lipopolysaccharide-stimulated cytokine secretion. Cytokine secretion in sepsis patients was generally less than 10% that in controls, independent of age, duration of sepsis, corticosteroid use, and nutritional status. Although differences existed between spleen and lung, flow cytometric analysis showed increased expression of selected inhibitory receptors and ligands and expansion of suppressor cell populations in both organs. Unique differences in cellular inhibitory molecule expression existed in immune cells isolated from lungs of sepsis patients vs cancer patients and vs transplant donors. Immunohistochemical staining showed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells. Conclusions Patients who die in the ICU following sepsis compared with patients who die of nonsepsis etiologies have biochemical, flow cytometric, and immunohistochemical findings consistent with immunosuppression. Targeted immune-enhancing therapy may be a valid approach in selected patients with sepsis.

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3.Immunosuppression in Sepsis
JAMA December 21, 2011, Vol 306, No. 23, pp 2618-9