Frédéric Lapostolle

Impact of Time to Treatment on Mortality After Prehospital Fibrinolysis or Primary Angioplasty Data From the CAPTIM Randomized Clinical Trial

Background—CAPTIM was a randomized trial comparing prehospital thrombolysis with transfer to an interventional facility (and, if needed, percutaneous intervention) with primary percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). Because the benefit of thrombolysis is maximal during the first 2 hours after symptom onset, and because prehospital thrombolysis can be implemented earlier than PCI, this analysis studied the relationship between the effect of assigned treatment and the time elapsed from symptom onset. Methods and Results—Randomization within 2 hours (n=460) or ≥2 hours (n=374) after symptom onset had no impact on the effect of treatment on the 30-day combined primary end point of death, nonfatal reinfarction, and disabling stroke. However, patients randomized <2 hours after symptom onset had a strong trend toward lower 30-day mortality with prehospital thrombolysis compared with those randomized to primary PCI (2.2% versus 5.7%, P =0.058), whereas mortality was similar in patients randomized ≥2 hours (5.9% versus 3.7%, P =0.47). There was a significant interaction between treatment effect and delay with respect to 30-day mortality (hazard ratio 4.19, 95% CI 1.033 to 17.004, P =0.045). Among patients randomized in the first 2 hours, cardiogenic shock was less frequent with lytic therapy than with primary PCI (1.3% versus 5.3%, P =0.032), whereas rates were similar in patients randomized later. Conclusions—Time from symptom onset should be considered when one selects reperfusion therapy in STEMI. Prehospital thrombolysis may be preferable to primary PCI for patients treated within the first 2 hours after symptom onset.

Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study.

BACKGROUND Although both prehospital fibrinolysis and primary angioplasty provide a clinical benefit over in-hospital fibrinolysis in acute myocardial infarction, they have not been directly compared. Our aim was to find out whether primary angioplasty was better than prehospital fibrinolysis. METHODS We did a randomised multicentre trial of 840 patients (of 1200 planned) who presented within 6 h of acute myocardial infarction with ST-segment elevation, initially managed by mobile emergency-care units. We assigned patients to prehospital fibrinolysis (n=419) with accelerated alteplase or primary angioplasty (n=421), and transferred all to a centre with access to emergency angioplasty. Our primary endpoint was a composite of death, non-fatal reinfarction, and non-fatal disabling stroke at 30 days. Analyses were by intention to treat. FINDINGS The median delay between onset of symptoms and treatment was 130 min in the prehospital-fibrinolysis group and 190 min (time to first balloon inflation) in the primary-angioplasty group. Rescue angioplasty was done in 26% of the patients in the fibrinolysis group. The rate of the primary endpoint was 8.2% (34 patients) in the prehospital-fibrinolysis group and 6.2% (26 patients) in the primary-angioplasty group (risk difference 1.96, 95% CI -1.53 to 5.46). 16 (3.8%) patients assigned prehospital fibrinolysis and 20 (4.8%) assigned primary angioplasty died (p=0.61). INTERPRETATION A strategy of primary angioplasty was not better than a strategy of prehospital fibrinolysis (with transfer to an interventional facility for possible rescue angioplasty) in patients presenting with early myocardial infarction.

Bivalirudin started during emergency transport for primary PCI

BACKGROUND Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.).

Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial

BACKGROUND Critically ill patients often require emergency intubation. The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients. METHODS In this randomised, controlled, single-blind trial, 655 patients who needed sedation for emergency intubation were prospectively enrolled from 12 emergency medical services or emergency departments and 65 intensive care units in France. Patients were randomly assigned by a computerised random-number generator list to receive 0.3 mg/kg of etomidate (n=328) or 2 mg/kg of ketamine (n=327) for intubation. Only the emergency physician enrolling patients was aware of group assignment. The primary endpoint was the maximum score of the sequential organ failure assessment during the first 3 days in the intensive care unit. We excluded from the analysis patients who died before reaching the hospital or those discharged from the intensive care unit before 3 days (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00440102. FINDINGS 234 patients were analysed in the etomidate group and 235 in the ketamine group. The mean maximum SOFA score between the two groups did not differ significantly (10.3 [SD 3.7] for etomidate vs 9.6 [3.9] for ketamine; mean difference 0.7 [95% CI 0.0-1.4], p=0.056). Intubation conditions did not differ significantly between the two groups (median intubation difficulty score 1 [IQR 0-3] in both groups; p=0.70). The percentage of patients with adrenal insufficiency was significantly higher in the etomidate group than in the ketamine group (OR 6.7, 3.5-12.7). We recorded no serious adverse events with either study drug. INTERPRETATION Our results show that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in critically ill patients, and should be considered in those with sepsis. FUNDING French Ministry of Health.

Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up

AIMS The CAPTIM (Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction) study found no evidence that a strategy of primary angioplasty was superior in terms of 30-day outcomes to a strategy of pre-hospital fibrinolysis with transfer to an interventional facility in patients managed early at the acute phase of an acute myocardial infarction. The present analysis was designed to compare both strategies at 5 years. METHODS AND RESULTS The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n = 421) or a pre-hospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n = 419). Long-term follow-up was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at 5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty group [HR 0.75 (95% CI, 0.50-1.14); P = 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI, 0.25-0.97); P = 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95% CI 0.59-1.75), P = 0.92]. CONCLUSION The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.

Randomized Study Comparing the "Sniffing Position" with Simple Head Extension for Laryngoscopic View in Elective Surgery Patients

BackgroundThe “sniffing position” is recommended for optimization of glottic visualization under direct laryngoscopy. However, no study to date has confirmed its superiority over simple head extension. In a prospective, randomized study, the authors compared the sniffing position with simple head extension in orotracheal intubation. MethodsThe study included 456 consecutive patients. The sniffing position was obtained by placement of a 7-cm cushion under the head of the patient. The extension position was obtained by simple head extension. The anesthetic procedure included two laryngoscopies without paralysis: the first was used for topical glottic anesthesia. During the second direct laryngoscopy, intubation of the trachea was performed. The head position was randomized as follows: group A was in the sniffing position during the first laryngoscopy and the extension position during the second; group B was in the extension position during the first laryngoscopy and the sniffing position during the second. Glottic exposure was assessed by the Cormack scale. ResultsThe sniffing position improved glottic exposure (decreased the Cormack grade) in 18% of patients and worsened it (increased the Cormack grade) in 11% of patients, in comparison with simple extension. The Cormack grade distribution was not significantly modified between the two groups. Multivariate analysis showed that reduced neck mobility and obesity were independently related to improvement in laryngoscopic view with application of the sniffing position. ConclusionsRoutine use of the sniffing position appears to provide no significant advantage over simple head extension for tracheal intubation in this setting. The sniffing position appears to be advantageous in obese and head extension–limited patients.

Family Presence during Cardiopulmonary Resuscitation

BACKGROUND The effect of family presence during cardiopulmonary resuscitation (CPR) on the family members themselves and the medical team remains controversial. METHODS We enrolled 570 relatives of patients who were in cardiac arrest and were given CPR by 15 prehospital emergency medical service units. The units were randomly assigned either to systematically offer the family member the opportunity to observe CPR (intervention group) or to follow standard practice regarding family presence (control group). The primary end point was the proportion of relatives with post-traumatic stress disorder (PTSD)-related symptoms on day 90. Secondary end points included the presence of anxiety and depression symptoms and the effect of family presence on medical efforts at resuscitation, the well-being of the health care team, and the occurrence of medicolegal claims. RESULTS In the intervention group, 211 of 266 relatives (79%) witnessed CPR, as compared with 131 of 304 relatives (43%) in the control group. In the intention-to-treat analysis, the frequency of PTSD-related symptoms was significantly higher in the control group than in the intervention group (adjusted odds ratio, 1.7; 95% confidence interval [CI], 1.2 to 2.5; P=0.004) and among family members who did not witness CPR than among those who did (adjusted odds ratio, 1.6; 95% CI, 1.1 to 2.5; P=0.02). Relatives who did not witness CPR had symptoms of anxiety and depression more frequently than those who did witness CPR. Family-witnessed CPR did not affect resuscitation characteristics, patient survival, or the level of emotional stress in the medical team and did not result in medicolegal claims. CONCLUSIONS Family presence during CPR was associated with positive results on psychological variables and did not interfere with medical efforts, increase stress in the health care team, or result in medicolegal conflicts. (Funded by Programme Hospitalier de Recherche Clinique 2008 of the French Ministry of Health; ClinicalTrials.gov number, NCT01009606.).

Family Presence During Cardiopulmonary Resuscitation

Patricia Jabre, M.D., Ph.D., Vanessa Belpomme, M.D., Elie Azoulay, M.D., Ph.D., Line Jacob, M.D., Lionel Bertrand, M.D., Frederic Lapostolle, M.D., Ph.D., Karim Tazarourte, M.D., Ph.D., Guillem Bouilleau, M.D., Virginie Pinaud, M.D., Claire Broche, M.D., Domitille Normand, M.S., Thierry Baubet, M.D., Ph.D., Agnes Ricard-Hibon, M.D., Ph.D., Jacques Istria, M.D., Alexandra Beltramini, M.D., Armelle Alheritiere, M.D., Nathalie Assez, M.D., Lionel Nace, M.D., Benoit Vivien, M.D., Ph.D., Laurent Turi, M.D., Stephane Launay, M.D., Michel Desmaizieres, M.D., Stephen W. Borron, M.D., Eric Vicaut, M.D., Ph.D., and Frederic Adnet, M.D., Ph.D.

Study of the "sniffing position" by magnetic resonance imaging

BackgroundThe “sniffing position” is widely considered essential to the performance of orotracheal intubation and has become the cornerstone of training in anesthesiology. However, the anatomic superiority of this patient head position has not been established. MethodsEight healthy young adult volunteers underwent magnetic resonance imaging scanning in three anatomic positions: head in neutral position, in simple extension, and in the “sniffing position” (neck flexed and head extended by means of a pillow). The following measurements were made on each scan: (1) the axis of the mouth (MA); (2) the pharyngeal axis (PA); (3) the laryngeal axis (LA); and (4) the line of vision. The various angles between these axes were defined: &agr; angle between the MA and PA, &bgr; angle between PA and LA, and &dgr; angle between line of vision and LA. ResultsBoth simple extension and sniffing positions significantly improved (P < 0.05) the &dgr; angle associated with best laryngoscopic view. Our results show that the &bgr; value increases significantly (P < 0.05) when the head position is shifted from the neutral position (&bgr; = 7 ± 6°) to the sniffing position (&bgr; = 13 ± 6°), and the &agr; value slightly (but significantly) decreases (from 87 ± 10° to 63 ± 11°;P < 0.05). Anatomic alignment of the LA, PA, and MA axes is impossible to achieve in any of the three positions tested. There were no significant differences between angles observed in simple extension and sniffing positions. ConclusionsThe sniffing position does not achieve alignment of the three important axes (MA, PA, and LA) in awake patients with normal airway anatomy.

Emergency Department Visits Caused by Adverse Drug Events

AbstractBackground: Adverse drug events (ADEs) are a substantial cause of hospital admissions. However, little is known about the incidence, preventability and severity of ADEs resulting in emergency department visits. To address this issue, we conducted a prospective survey in emergency departments of French public hospitals. Methods: This study was performed over two periods of 1 week each, one in June 1999 and one in December 1999, in emergency departments of five university hospitals and five general hospitals throughout France. All patients aged ≥15 years presenting with medical complaints were included in the study. Trauma patients, those with gynaecological conditions and those with alcohol intoxication or intentional drug poisoning were excluded from the study. Each patient was assessed by two local emergency physicians to determine whether the visit was the result of an ADE. All medical records were subsequently validated by an independent group of medical lecturers in iatrogenic disorders. Results: Out of a total of 1937 patients consulting, 1562 were taking at least one drug during the previous week and were included for analysis; 328 (21%; 95% CI 19, 23) of these patients consulted an emergency physician because of an ADE. Patients with ADEs were older than those without (mean age 63.5 vs 54.8 years; p < 0.0001). Furthermore, ADE patients were more likely to have a higher severity presentation than the non-ADE group (p = 0.019). The number of drug exposures was significantly higher in patients with an ADE than in those without (mean number of medications 5.17 vs 3.82; p < 0.0001). On multivariate analysis, only age and the number of medications taken were significantly associated with adverse events. In total, 410 drugs were incriminated in the occurrence of 328 ADEs. The most frequently incriminated drug classes were: (i) psychotropic agents (n = 84; 20.5%); (ii) diuretics (n = 48; 11.7%), anticoagulants (n = 38; 9.3%) and other cardiovascular drugs (n = 63; 15.4%); and (iii) analgesics, including NSAIDs (n = 57; 13.9%). Preventability could be assessed in 280 of the 328 cases. In 106 cases (37.9%), the ADE was judged to be preventable. Conclusion: ADEs leading to emergency department visits are frequent, and many are preventable, confirming that there is a need to develop prevention strategies.