Pre-hospital ECMO

August 29, 2011 by  
Filed under Acute Med, All Updates, EMS, ICU, Kids, Resus

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Two cases are reported of the pre-hospital institution of venoarterial extracorporeal membrane oxygenation (ECMO) for patients in cardiac arrest. One was from France and the other from Germany – both countries with mature physician-staffed pre-hospital systems. The two cases were a 9 yr old drowning victim1 and a 48 year old marathon runner2. They each received BLS then ACLS then ECMO, and both went from asystole to sinus rhythm after the institution of ECMO. Sadly both failed to neurologically recover and died in hospital.

If irreversible anoxic encephalopathy could be detected in the field, patients could be better selected for this intervention. An editorialist3 states:


Until we have a hand held device which can measure neuronal integrity on a cellular level in the field we must use our best judgement, and in many cases give the patient the benefit of the doubt by cannulating them, cooling for 24 h and then making a neurological assessment and withdrawing ECLS if necessary.

Other issues to consider are:

  • Can society afford this level of intervention?
  • Could this intervention, when associated with brain death, result in sufficiently recovered organs for transplantation?
  • How can the infrastructure be created to enable rapid institution of pre-hospital ECMO?

I suspect as the equipment becomes even more portable and self-maintaining, pre-hospital / retrieval physicians already expert in critical care interventions such as seldinger-guided vascular access will be the ones instituting this therapy. In the meantime, we await evidence of outcome benefit and some objective means of case selection.

1. Out-of-hospital extracorporeal life support for cardiac arrest—A case report
Resuscitation. 2011 Sep;82(9):1243-5

2. Out-of-hospital extra-corporeal life support implantation during refractory cardiac arrest in a half-marathon runner
Resuscitation. 2011 Sep;82(9):1239-42

3. Community extracorporeal life support for cardiac arrest – When should it be used?
Resuscitation. 2011 Sep;82(9):1117

Mouth-to-nose breathing

August 25, 2011 by  
Filed under Acute Med, All Updates, EMS, Resus

Interesting – mouth to nose breathing was more effective than mouth-to-mouth in simulated resuscitations using anaesthetised, apnoeic patients:


BACKGROUND: The authors hypothesized that mouth ventilation by a resuscitator via the nasal route ensures a more patent airway and more effective ventilation than does ventilation via the oral route and therefore would be the optimal manner to ventilate adult patients in emergencies, such as during cardiopulmonary resuscitation. They tested the hypothesis by comparing the effectiveness of mouth-to-nose breathing (MNB) and mouth-to-mouth breathing (MMB) in anesthetized, apneic, adult subjects without muscle paralysis.

METHODS: Twenty subjects under general anesthesia randomly received MMB and MNB with their heads placed first in a neutral position and then an extended position. A single operator performed MNB and MMB at the target breathing rate of 10 breaths/min, inspiratory:expiratory ratio 1:2 and peak inspiratory airway pressure 24 cm H₂O. A plethysmograph was used to measure the amplitude change during MMB and MNB. The inspiratory and expiratory tidal volumes during MMB and MNB were calculated retrospectively using the calibration curve.

RESULTS: All data are presented as medians (interquartile ranges). The rates of effective ventilation (expired volume > estimated anatomic dead space) during MNB and MMB were 91.1% (42.4-100%) and 43.1% (42.5-100%) (P < 0.001), and expired tidal volume with MMB 130.5 ml (44.0-372.8 ml) was significantly lower than with MNB 324.5 ml (140.8-509.0 ml), regardless of the head position (P < 0.001).

CONCLUSIONS: Direct mouth ventilation delivered exclusively via the nose is significantly more effective than that delivered via the mouth in anesthetized, apneic adult subjects without muscle paralysis. Additional studies are needed to establish whether using this breathing technique during emergency situations will improve patient outcomes.

Effectiveness of breathing through nasal and oral routes in unconscious apneic adult human subjects: a prospective randomized crossover trial
Anesthesiology. 2011 Jul;115(1):129-35

Glutamine in ICU

August 24, 2011 by  
Filed under All Updates, ICU

Of interest to intensivists….


Background: Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi-centric, double-blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation.

Methods: Patients (n=413) given nutrition by an enteral and/or a parenteral route with the aim of providing full nutrition were included within 72 h after ICU admission. Glutamine was supplemented as i.v. l-alanyl-l-glutamine, 0.283 g glutamine/kg body weight/24 h for the entire ICU stay. Placebo was saline in identical bottles. All included patients were considered as intention-to-treat patients. Patients given supplementation for >3 days were considered as predetermined per protocol (PP) patients.

Results: There was a lower ICU mortality in the treatment arm as compared with the controls in the PP group, but not at 6 months. For change in the SOFA scores, no differences were seen, 1 (0,3) vs. 2 (0.4), P=0.792, for the glutamine group and the controls, respectively.

Conclusion: In summary, a reduced ICU mortality was observed during i.v. glutamine supplementation in the PP group. The pragmatic design of the study makes the results representative for a broad range of ICU patients.

Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients
Acta Anaesthesiol Scand. 2011 Aug;55(7):812-818

Nitric oxide for right ventricular cardiogenic shock

August 21, 2011 by  
Filed under Acute Med, All Updates, ICU, Resus

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A case report describes a patient with right ventricular cardiogenic shock due to a dissected right coronary artery1. There was deterioration despite fluid, inotropic and intraaortic balloon pump therapy, followed by improvement with the introduction of inhaled nitric oxide (iNO) at 12 to 15 ppm (a selective pulmonary vasodilator), to the point where vasoactive medication was withdrawn. The cessation of iNO was associated with deterioration which resolved with its reintroduction. It was more gradually withdrawn and the patient made a good recovery.

The rationale for the use of iNO in patients with acute RV heart failure due to MI is afterload reduction without systemic hypotension.

It has been shown to improve haemodynamics in RV MI patients with cardiogenic shock in a previous case series2 (abstract below) in which its effects on pulmonary vasodilation are thought be beneficial. In RV MI with shock increased pulmonary vascular tone is postulated to result from the following mechanisms:

  • A low cardiac output results in a decreased mixed venous blood oxygen content, which enhances pulmonary artery vasoconstriction.
  • The intravenous infusion of alpha-adrenergic vasoconstrictors can contribute to pulmonary vasoconstriction.
  • Mechanical ventilation with positive end-expiratory pressure can increase the pulmonary vascular resistance through compression of the pulmonary vasculature.
  • Interstitial pulmonary edema, which may occur in some patients with coexisting LV dysfunction, can also cause pulmonary constriction

OBJECTIVES: We sought to determine whether or not inhaled nitric oxide (NO) could improve hemodynamic function in patients with right ventricular myocardial infarction (RVMI) and cardiogenic shock (CS).

BACKGROUND: Inhaled NO is a selective pulmonary vasodilator that can decrease right ventricular afterload.

METHODS: Thirteen patients (7 males and 6 females, age 65 +/- 3 years) presenting with electrocardiographic, echocardiographic, and hemodynamic evidence of acute inferior myocardial infarction associated with RVMI and CS were studied. After administration of supplemental oxygen (inspired oxygen fraction [F(i)O(2)] = 1.0), hemodynamic measurements were recorded before, during inhalation of NO (80 ppm at F(i)O(2) = 0.90) for 10 min, and 10 min after NO inhalation was discontinued (F(i)O(2) = 1.0).

RESULTS: Breathing NO decreased the mean right atrial pressure by 12 +/- 3%, mean pulmonary arterial pressure by 13 +/- 2%, and pulmonary vascular resistance by 36 +/- 8% (all p < 0.05). Nitric oxide inhalation increased the cardiac index by 24 +/- 11% and the stroke volume index by 23 +/- 12% (p < 0.05). The NO administration did not change systemic arterial or pulmonary capillary wedge pressures. Contrast echocardiography identified three patients with a patent foramen ovale and right-to-left shunt flow while breathing at F(i)O(2) = 1.0. Breathing NO decreased shunt flow by 56 +/- 5% (p < 0.05) and was associated with markedly improved systemic oxygen saturation.

CONCLUSIONS: Nitric oxide inhalation results in acute hemodynamic improvement when administered to patients with RVMI and CS.

1. Use of inhaled nitric oxide in the treatment of right ventricular myocardial infarction
Am J Emerg Med. 2011 May;29(4):473.e3-5

2. Hemodynamic effects of inhaled nitric oxide in right ventricular myocardial infarction and cardiogenic shock
J Am Coll Cardiol. 2004 Aug 18;44(4):793-8

Surgeons and trauma teams

August 19, 2011 by  
Filed under All Updates, EMS, Resus, Trauma

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There can be issues associated with calling surgeons to trauma team activations in the ED, including interruption to the surgeon’s other duties, and the absence of anything useful for the surgeon to do, when most blunt trauma patients are managed by emergency physicians, intensivists, and orthopaedic surgeons, with a growing input from interventional radiologists. At one American major trauma centre for example, emergency operation by a trauma surgeon for blunt trauma averages once every 7 weeks for adults and less than once every 3 years for children1.

While there are many surgeons who are passionate about trauma care and excellent in the non-operative aspects of trauma management, there are probably more who would welcome measures to reduce the need to attend ED for all trauma team activations. Of course no triage tool is perfect: they will always have to trade sensitivity against specificity. One such tool from the Loma Linda University Medical Center uses the simple criteria of penetrating trauma, systolic blood pressure, and heart rate. These pertain to pre-hospital measurement and therefore the surgeon can be activated prior to patient arrival.

This triage tool performed better than the American College of Surgeons’ “major resuscitation” trauma triage criteria2:


STUDY OBJECTIVE: Trauma centers use “secondary triage” to determine the necessity of trauma surgeon involvement. A clinical decision rule, which includes penetrating injury, an initial systolic blood pressure less than 100 mm Hg, or an initial pulse rate greater than 100 beats/min, was developed to predict which trauma patients require emergency operative intervention or emergency procedural intervention (cricothyroidotomy or thoracotomy) in the emergency department. Our goal was to validate this rule in an adult trauma population and to compare it with the American College of Surgeons’ major resuscitation criteria.

METHODS: We used Level I trauma center registry data from September 1, 1995, through November 30, 2008. Outcomes were confirmed with blinded abstractors. Sensitivity, specificity, and 95% confidence intervals (CIs) were calculated.

RESULTS: Our patient sample included 20,872 individuals. The median Injury Severity Score was 9 (interquartile range 4 to 16), 15.3% of patients had penetrating injuries, 13.5% had a systolic blood pressure less than 100 mm Hg, and 32.5% had a pulse rate greater than 100 beats/min. Emergency operative intervention or procedural intervention was required in 1,099 patients (5.3%; 95% CI 5.0% to 5.6%). The sensitivities and specificities of the rule and the major resuscitation criteria for predicting emergency operative intervention or emergency procedural intervention were 95.6% (95% CI 94.3% to 96.8%) and 56.1% (95% CI 55.4% to 56.8%) and 85.5% (95% CI 83.3% to 87.5%) and 80.9% (95% CI 80.3% to 81.4%), respectively.

CONCLUSION: This new rule was more sensitive for predicting the need for emergency operative intervention or emergency procedural intervention directly compared with the American College of Surgeons’ major resuscitation criteria, which may improve the effectiveness and efficiency of trauma triage.

Although not mentioned in the abstract, the study also included assessment of refinements of the Loma Linda Rule based on different cutoffs of heart rate and blood pressure. Once such refinement that included penetrating injury to the torso and less conservative physiological criteria (systolic blood pressure <90 mm Hg and pulse rate >110 beats/min) resulted in a slightly lower sensitivity, with a dramatic improvement in specificity compared with the original Loma Linda Rule.

A good point is made by Steve Green in his accompanying editoral3:


A possibility is that emergency physicians supervising out-of-hospital radio calls can predict the need for surgeon presence just as accurately (or perhaps more accurately) as any of these rules. After all, judgment is the time-tested mechanism by which emergency physicians summon all other consultants for all other conditions.

Unfortunately for many UK and Australasian centres, the challenge that remains is not deciding when to call the surgeon, but getting one when you do call, preferable one who is not committed to an elective operating list and one who has some training and experience in trauma surgery.

1. Clinical decision rules for secondary trauma triage: predictors of emergency operative management.
Ann Emerg Med. 2006 Feb;47(2):135

2. Validation and refinement of a rule to predict emergency intervention in adult trauma patients
Ann Emerg Med. 2011 Aug;58(2):164-71

3. Trauma is occasionally a surgical disease: how can we best predict when?
Ann Emerg Med. 2011 Aug;58(2):172-177

Ultrasound to detect difficult laryngoscopy

August 17, 2011 by  
Filed under All Updates, ICU, Resus, Ultrasound

A pilot study suggests sonographic measurements of neck soft tissue thickness may predict difficult laryngoscopy. Laryngoscopy was difficult in patients with increased thickness of the anterior neck soft tissue at the level of the hyoid bone and thyrohyoid membrane. The authors suggest that anterior neck soft tissue thickness cutoff value of 2.8 cm at the thyrohyoid membrane level can potentially be used to detect difficult laryngoscopy, but that this would require further validation since in this pilot study there were only six subjects in the difficult laryngoscopy group.


Objectives:  Prediction of difficult laryngoscopy in emergency care settings is challenging. The preintubation clinical screening tests may not be applied in a large number of emergency intubations due to the patient’s clinical condition. The objectives of this study were 1) to determine the utility of sonographic measurements of thickness of the tongue, anterior neck soft tissue at the level of the hyoid bone, and thyrohyoid membrane in distinguishing difficult and easy laryngoscopies and 2) to examine the association between sonographic measurements (thickness of tongue and anterior neck soft tissue) and difficult airway clinical screening tests (modified Mallampati score, thyromental distance, and interincisor gap).

Methods:  This was a prospective observational study at an academic medical center. Adult patients undergoing endotracheal intubation for an elective surgical procedure were included. The investigators involved in data collection were blinded to each other’s assessments. Demographic variables were collected preoperatively. The clinical screening tests to predict a difficult airway were performed. The ultrasound (US) measurements of tongue and anterior neck soft tissue were obtained. The laryngoscopic view was graded using Cormack and Lehane classification by anesthesia providers on the day of surgery. To allow for comparisons between difficult airway and easy airway groups, a two-sided Student’s t-test and Fisher’s exact test were employed as appropriate. Spearman’s rank correlation coefficients were used to examine the association between screening tests and sonographic measurements.

Results:  The mean (±standard deviation [SD]) age of 51 eligible patients (32 female, 19 male) was 53.1 (±13.2) years. Six of the 51 patients (12%, 95% confidence interval [CI] = 3% to 20%) were classified as having difficult laryngoscopy by anesthesia providers. The distribution of laryngoscopy grades for all subjects was 63, 25, 4, and 8% for grades 1, 2, 3, and 4, respectively. In this study, 83% of subjects with difficult airways were males. No other significant differences were noted in the demographic variables and difficult airway clinical screening tests between the two groups. The sonographic measurements of anterior neck soft tissue were greater in the difficult laryngoscopy group compared to the easy laryngoscopy group at the level of the hyoid bone (1.69, 95% CI = 1.19 to 2.19 vs. 1.37, 95% CI = 1.27 to 1.46) and thyrohyoid membrane (3.47, 95% CI = 2.88 to 4.07 vs. 2.37, 95% CI = 2.29 to 2.44). No significant correlation was found between sonographic measurements and clinical screening tests.

Conclusions:  This pilot study demonstrated that sonographic measurements of anterior neck soft tissue thickness at the level of hyoid bone and thyrohyoid membrane can be used to distinguish difficult and easy laryngoscopies. Clinical screening tests did not correlate with US measurements, and US was able to detect difficult laryngoscopy, indicating the limitations of the conventional screening tests for predicting difficult laryngoscopy.

Pilot Study to Determine the Utility of Point-of-care Ultrasound in the Assessment of Difficult Laryngoscopy
Acad Emerg Med. 2011 Jul;18(7):754-8

Ultrasound-Guided Radial Artery Catheterization

August 16, 2011 by  
Filed under All Updates, ICU, Resus, Ultrasound

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In case you needed some evidence – a systematic review supports ultrasound guidance as a means of improving insertion success of radial artery catheters


BACKGROUND: Ultrasound guidance commonly is used for the placement of central venous catheters (CVCs). The Agency for Healthcare Research and Quality recommends the use of ultrasound for CVC placement as one of its 11 practices to improve patient care. Despite increased access to portable ultrasound machines and comfort with ultrasound-guided CVC access, fewer clinicians are familiar with ultrasound-guided techniques of arterial catheterization. The goal of this systematic review and meta-analysis was to determine the utility of real-time two-dimensional ultrasound guidance for radial artery catheterization.

METHODS: A comprehensive literature search of Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials by two independent reviewers identified prospective, randomized controlled trials comparing ultrasound guidance with traditional palpation techniques of radial artery catheterization. Data were extracted on study design, study size, operator and patient characteristics, and the rate of first-attempt success. A meta-analysis was constructed to analyze the data.

RESULTS: Four trials with a total of 311 subjects were included in the review, with 152 subjects included in the palpation group and 159 in the ultrasound-guided group. Compared with the palpation method, ultrasound guidance for arterial catheterization was associated with a 71% improvement in the likelihood of first-attempt success (relative risk, 1.71; 95% CI, 1.25-2.32).

CONCLUSIONS: The use of real-time two-dimensional ultrasound guidance for radial artery catheterization improved first-pass success rate.

Ultrasound-Guided Catheterization of the Radial Artery
Chest. 2011 Mar;139(3):524-9

Early CT may rule out subarachnoid haemorrhage

August 15, 2011 by  
Filed under Acute Med, All Updates, ICU, Resus

A multicentre Canadian study challenges the practice of routine lumbar puncture after negative CT in patients with suspected subarachnoid haemorrhage. CT scanning within six hours was highly sensitive, although a few cases of initially misinterpreted CTs “illustrate the importance of having a qualified radiologist with a high level of skill interpreting the head scans in a timely manner“.

Nearly 2% of patients were lost to all follow-up; the authors point out that even if a quarter of these patients could have experienced a subarachnoid haemorrhage, the corresponding negative likelihood ratio for a computed tomography performed within six hours rises to only 0.024 (0.007 to 0.07). They assert:

Such a likelihood ratio could be incorporated into the informed discussion surrounding the risks and benefits of lumbar puncture after negative results on computed tomography for this diagnosis

They point out that when CT imaging is obtained more than six hours after headache onset, clinicians should continue to be cautious because of the decreasing sensitivity for subarachnoid haemorrhage beyond this time.


Objective To measure the sensitivity of modern third generation computed tomography in emergency patients being evaluated for possible subarachnoid haemorrhage, especially when carried out within six hours of headache onset.

Design Prospective cohort study. Setting 11 tertiary care emergency departments across Canada, 2000-9.

Participants Neurologically intact adults with a new acute headache peaking in intensity within one hour of onset in whom a computed tomography was ordered by the treating physician to rule out subarachnoid haemorrhage.

Main outcome measures Subarachnoid haemorrhage was defined by any of subarachnoid blood on computed tomography, xanthochromia in cerebrospinal fluid, or any red blood cells in final tube of cerebrospinal fluid collected with positive results on cerebral angiography.

Results Of the 3132 patients enrolled (mean age 45.1, 2571 (82.1%) with worst headache ever), 240 had subarachnoid haemorrhage (7.7%). The sensitivity of computed tomography overall for subarachnoid
haemorrhage was 92.9% (95% confidence interval 89.0% to 95.5%), the specificity was 100% (99.9% to 100%), the negative predictive value was 99.4% (99.1% to 99.6%), and the positive predictive value was 100% (98.3% to 100%). For the 953 patients scanned within six hours of headache onset, all 121 patients with subarachnoid haemorrhage were identified by computed tomography, yielding a sensitivity of 100% (97.0% to 100.0%), specificity of 100% (99.5% to 100%), negative predictive value of 100% (99.5% to 100%), and positive predictive value of 100% (96.9% to 100%).

Conclusion Modern third generation computed tomography is extremely sensitive in identifying subarachnoid haemorrhage when it is carried out within six hours of headache onset and interpreted by a qualified radiologist

Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study
BMJ. 2011 Jul 18;343:d4277

CRASH-2 and head injury

August 14, 2011 by  
Filed under All Updates, ICU, Resus, Trauma

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The overall effect of the antifibrinolytic drug tranexamic acid on outcome from major trauma was assessed in the CRASH-2 trial, reported here and here. Its effect on a nested cohort of 270 patients from the trial who had traumatic brain injury has now been published1.

Previous evaluation in nontraumatic subarachnoid haemorrhage patients showed tranexamic acid to be associated with cerebral ischaemia, whereas in CRASH-2 (in which a lower dose of tranexamic acid was used) there was a trend to fewer ischaemic lesions as well as smaller haematoma growth and decreased mortality. None of these outcomes were statistically significant so further research is warranted.

An accompanying editorial2 states:

…the CRASH-2 study also justifies a re-evaluation of the possible benefit of low dose short term TXA in patients with other types of intracranial haemorrhage. Many patients with aneurysmal subarachnoid haemorrhage still have to wait for one or two days before the aneurysm is occluded. In addition, at least 30% of patients with spontaneous intracerebral haemorrhage experience substantial haematoma growth in the first 24 hours after the onset of the haemorrhage. As well as the CRASH-2 trial we therefore need new trials investigating short course low dose TXA in patients with aneurysmal subarachnoid haemorrhage and intracerebral haemorrhage.

It looks like considerable enthusiasm for this drug will be around for a while. I look forward to more outcome data, particularly in regard to this challenging group of patients with traumatic and non-traumatic intracranial bleeding.


OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury.

METHODS: A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury.

INTERVENTIONS: Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo.

MAIN OUTCOME MEASURES: Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume.

RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)).

CONCLUSIONS: This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population

1. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)
BMJ. 2011 Jul 1;343:d379 (free text available)

2. Tranexamic acid for traumatic brain injury
BMJ. 2011 Jul 1;343:d3958

What do I do with a high sensitivity troponin?

August 13, 2011 by  
Filed under Acute Med, All Updates, Guidelines, Resus

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Newer high-sensitivity troponin tests can be positive in patients who would have negative tests with the ‘traditional’ assay, which can result in confusion about what to do with the patient, particularly those patients without an obvious cardiac presentation. A recent study1 shows that the majority of patients that fall into this group had non-cardiac discharge diagnoses.


Background: High sensitivity troponin T (hsTnT) detects lower levels of troponin T with greater precision than the 4th generation (cTnT) assay. However, the clinical implications of this are uncertain.

Objectives: Primary: Describe the proportion of patients who test ‘positive’ with hsTnT but negative with cTnT. Secondary: Determine proportion in each group with an adverse event (representation, AMI or died) within 90 days of the index test.

Method: 161 patients samples were tested with cTnT and hsTNT assays. McNemar’s test was used to compare paired samples. Electronic medical records were reviewed, with discharge diagnosis and 90 day outcomes determined blind to hsTnT results. Patients were then classified as ‘TnT negative’ (hsTnT was <0.014 mcg/mL), 'new positive' (hsTnT was ≥0.014 mcg/mL and cTnT <0.03 mcg/mL) and 'TnT positive' (cTNT was ≥0.03 mcg/mL)

Results: Positive results more than doubled with the hsTnT assay (50% vs 22%, P < 0.001). 81 patients were ‘TnT negative’, 44 were ‘new positive’ and 36 ‘cTnT positive’. The discharge diagnosis for ‘new positives’ was AMI in 4 (9%), other cardiac in 13 (30%) and non-cardiac in 27 (61%). At 90 days adverse events occurred in 30%, 54% and 50% of the groups respectively. There were no late cases of AMI or cardiovascular death in ‘new positive’ patients.

Conclusion: Many patients with diagnoses other than AMI will have hsTNT above the reference level. Indiscriminate testing with hsTnT might lead to more patients requiring serial troponin testing and/or invasive further tests, which will have process and resource implications for EDs and health services.

An accompanying editorial2 highlights that:

Elevations are seen in pathological conditions, including structural heart disease, renal impairment and pulmonary embolism, but might also be seen in extreme exertion, such as marathon runners. It is now clear that when using a highly sensitive assay, circulating levels of troponin will be detected in many normal people.

The editorial makes the interesting observation that the duration of rise may help elucidate the cause; ischaemic elevation of troponin falls rapidly, since the rise might be due to the release of small amounts of troponin that exist free within the cytoplasm, in contrast to the more persistent elevation seen with myocardial necrosis. The editorialist provides the following caution:


Overall, our practice for ordering troponin will need to be urgently reviewed. Single troponin values will continue to be of little to no use in defining disease states in the ED. Identifying a chronic versus an acute elevation will only be revealed by serial troponin testing. The time interval between testing is currently contentious.

High sensitivity troponins are referred to in the newly published 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the Management of Acute Coronary Syndromes (full text link below)3:

RECOMMENDED PROTOCOL FOR TROPONIN TESTING USING HIGH SENSITIVITY ASSAYS IN “RULING-OUT” ACS
  • All patients with a suspected ACS should undergo troponin testing on arrival at ED to ‘rule in’ ACS within the differential diagnosis
  • For a patient with a positive troponin result or a change in troponin levels over time, neither ACS nor other significant pathology (e.g. pulmonary embolus, aortic dissection, and sepsis) can be excluded. These patients are at higher risk of subsequent events. A positive result should be considered within the entire clinical context (history, examination, ECG findings and other investigations). Further investigations directed at all plausible clinical diagnoses should be considered and, if ACS is thought to be the likely cause, these patients may require cardiology assessment.
  • All patients with a negative result should undergo repeat testing 3–4 hours later.
  • The testing interval to ‘rule out’ MI may be reduced to 3 hours, provided that one sample is taken at least 6 hours after symptom onset:
  • Patients with a negative result at 3 hours after presentation and at least 6 hours after the onset of pain should be considered for early assessment by non-invasive anatomic or functional testing, as determined by local availability.
  • For patients presenting more than 6 hours after pain onset, a single high sensitivity troponin assay is sufficient to rule out myocardial infarction in the absence of ongoing chest pain.

High sensitivity troponin assays have an increased sensitivity for the detection of “myonecrosis”, but a reduced specificity for the diagnosis of “MI”. A positive result (≥99th centile for reference population OR where there is a change of ≥50% above an initial baseline level) should be interpreted in the context of the entire clinical presentation and does not necessarily represent an indication for coronary angiography. The management MI secondary to other conditions (e.g. anaemia, thyrotoxicosis, and sepsis) should be primarily directed at those conditions.
The finding of troponin concentrations that remain stable over time suggests that the presence of troponin is due to chronic disease. Acute exacerbations of chronic disease that result in elevated troponin levels can mimic an MI release pattern.

1. Clinical diagnosis and outcomes for Troponin T ‘positive’ patients assessed by a high sensitivity compared with a 4th generation assay
Emerg Med Australas. 2011 Aug;23(4):490-501

2. Troponin: A risk-defining biomarker for emergency department physicians
Emerg Med Australas. 2011 Aug;23(4):391-4

3. 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the Management of Acute Coronary Syndromes
Heart, Lung and Circulation 2011 Aug;28(8):487-502 Free Full Text

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