Spyros D. Mentzelopoulos

Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest

BACKGROUND Animal data on cardiac arrest showed improved long-term survival with combined vasopressin-epinephrine. In cardiac arrest, cortisol levels are relatively low during and after cardiopulmonary resuscitation. We hypothesized that combined vasopressin-epinephrine and corticosteroid supplementation during and after resuscitation may improve survival in refractory in-hospital cardiac arrest. METHODS We conducted a single-center, prospective, randomized, double-blind, placebo-controlled, parallel-group trial. We enrolled 100 consecutive patients with cardiac arrest requiring epinephrine according to current resuscitation guidelines. Patients received either vasopressin (20 IU per cardiopulmonary resuscitation cycle) plus epinephrine (1 mg per resuscitation cycle) (study group; n = 48) or isotonic sodium chloride solution placebo plus epinephrine (1 mg per resuscitation cycle) (control group; n = 52) for the first 5 resuscitation cycles after randomization, followed by additional epinephrine if needed. On the first resuscitation cycle, study group patients received methylprednisolone sodium succinate (40 mg) and controls received saline placebo. Postresuscitation shock was treated with stress-dose hydrocortisone sodium succinate (300 mg daily for 7 days maximum, with gradual taper) (27 patients in the study group) or saline placebo (15 patients in the control group). Primary end points were return of spontaneous circulation for 15 minutes or longer and survival to hospital discharge. RESULTS Study group patients vs controls had more frequent return of spontaneous circulation (39 of 48 patients [81%] vs 27 of 52 [52%]; P = .003) and improved survival to hospital discharge (9 [19%] vs 2 [4%]; P = .02). Study group patients with postresuscitation shock vs corresponding controls had improved survival to hospital discharge (8 of 27 patients [30%] vs 0 of 15 [0%]; P = .02), improved hemodynamics and central venous oxygen saturation, and more organ failure-free days. Adverse events were similar in the 2 groups. CONCLUSION In this single-center trial, combined vasopressin-epinephrine and methylprednisolone during resuscitation and stress-dose hydrocortisone in postresuscitation shock improved survival in refractory in-hospital cardiac arrest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00411879.

Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination. OBJECTIVE To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility). INTERVENTIONS Patients received either vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methylprednisolone (40 mg) and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73). MAIN OUTCOMES AND MEASURES Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2. RESULTS Follow-up was completed in all resuscitated patients. Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P = .005) and survival to hospital discharge with CPC score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; P = .02). Patients in the VSE group with postresuscitation shock vs corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; P = .02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the 2 groups. CONCLUSION AND RELEVANCE Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00729794.

Prone position reduces lung stress and strain in severe acute respiratory distress syndrome

The present authors hypothesised that in severe acute respiratory distress syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e. transpulmonary pressure (PL)) and strain of lung parenchyma (i.e. tidal volume (VT)/end-expiratory lung volume (EELV) ratio), which constitute major ventilator-induced lung injury determinants. The authors sought to determine whether potential pronation benefits are maintained in post-prone semirecumbent (SRPP) posture under pressure-volume curve-dependent optimisation of positive end-expiratory pressure (PEEP). A total of 10 anesthetised/paralysed, mechanically ventilated (VT = 9.0±0.9 mL·kg−1 predicted body weight; flow = 0.91±0.04 L·s−1; PEEP = 9.4±1.3 cmH2O) patients with early/severe ARDS were studied in pre-prone semirecumbent (SRBAS), prone, and SRPP positions. Partitioned respiratory mechanics were determined during iso-flow (0.91 L·s−1) experiments (VT varied within 0.2–1.0 L), along with haemodynamics, gas exchange, and EELV. Compared with SRBAS, pronation/SRPP resulted in reduced peak/plateau PL at VTs≥0.6 L; static lung elastance and additional lung resistance decreased and chest wall elastance (in prone position) increased; EELV increased (23–33%); VT/EELV decreased (27–33%); arterial oxygen tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved (21–43/10–14%, respectively), and shunt fraction/physiological dead space decreased (21–50/20–47%, respectively). In early/severe acute respiratory distress syndrome, pronation under positive end-expiratory pressure optimisation may reduce ventilator-induced lung injury risk. Pronation benefits may be maintained in post-prone semirecumbent position.

Vasopressin for cardiac arrest: Meta-analysis of randomized controlled trials☆

BACKGROUND Prior meta-analyses-reported results of randomised controlled trials (RCTs) published between 1997 and 2004 failed to show any vasopressin-related benefit in cardiac arrest. Based on new RCT-data and a hypothesis of a potentially increased vasoconstricting efficacy of vasopressin, we sought to determine whether the cumulative, current evidence supports or refutes an overall and/or selective benefit for vasopressin regarding sustained restoration of spontaneous circulation (ROSC), long-term survival, and neurological outcome. METHODS Two reviewers independently searched PubMed, EMBASE, and Cochrane Database for RCTs assigning adults with cardiac arrest to treatment with a vasopressin-containing regimen (vasopressin-group) vs adrenaline (epinephrine) alone (control-group) and reporting on long-term outcomes. Data from 4475 patients in 6 high-methodological quality RCTs were analyzed. Subgroup analyses were conducted according to initial cardiac rhythm and time from collapse to drug administration (T(DRUG))<20 min. RESULTS Vasopressin vs. control did not improve overall rates of sustained ROSC, long-term survival, or favourable neurological outcome. However, in asystole, vasopressin vs. control was associated with higher long-term survival {odds ratio (OR)=1.80, 95% confidence interval (CI)=1.04-3.12, P=0.04}. In asystolic patients of RCTs with average T(DRUG)<20 min, vasopressin vs. control increased the rates of sustained ROSC (data available from 2 RCTs; OR=1.70, 95% CI=1.17-2.47, P=0.005) and long-term survival (data available from 3 RCTs; OR=2.84, 95% CI=1.19-6.79, P=0.02). CONCLUSIONS Vasopressin use in the resuscitation of cardiac arrest patients is not associated with any overall benefit or harm. However, vasopressin may improve the long-term survival of asystolic patients, especially when average T(DRUG) is <20 min.

Ethik der Reanimation und Entscheidungen am Lebensende

Der unerwartete Kreislaufstillstand stellt ein Ereignis dar, das haufig verheerende Folgen fur die betroffene Person, Fami-lie und Freunde mit sich bringt. Wahrend einige Wiederbelebungsversuche erfolg-reich mit einem guten Langzeit-Outcome einhergehen, trifft dies fur die Mehrzahl der Falle trotz groser Anstrengungen und einiger Verbesserungen in der Versorgung von Herz-Kreislauf-Patienten wahrend des letzten Jahrzehnts nicht zu.Professionelle Helfer sind verpflichtet, alles Notige zu tun, um Leben zu schut-zen und zu bewahren. Die Gesellschaft als Ganzes, besonders aber Rettungsdienst-personal, Krankenhauser und andere Ein-richtungen des Gesundheitswesens mus-sen fur den Fall des plotzlichen Kreislauf-stillstands geeignete Masnahmen planen, organisieren und anwenden. Damit sind meist der Einsatz vieler Ressourcen und hohe Kosten verbunden, v. a. in den wohl-habenderen Landern. Technische Neue-rungen, medizinische Evidenz und stei-gende Erwartungen der Offentlichkeit haben ethische Uberlegungen zu einem wichtigen Bestandteil jeglicher Interven-tion oder Entscheidung am Lebensende werden lassen. Dazu gehort, durch geeig-nete Allokation der verfugbaren Ressour-cen das bestmogliche Ergebnis fur den einzelnen Patienten, die Angehorigen und die gesamte Gesellschaft zu erzielen.Um sicherzustellen, dass Entschei-dungen, mit Wiederbelebungsversuchen zu beginnen oder nicht, angemessen sind und dass Patienten mit Wurde behandelt werden, bedarf es einiger Erwagungen. Derartige Entscheidungen sind komplex und konnen durch individuelle, internati-onal und lokal kulturelle, rechtliche, traditi-onelle, religiose, soziale und okonomische Faktoren beeinflusst werden [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. Zuweilen konnen die Ent-schlusse im Voraus getroffen werden, aber haufig mussen diese schwierigen Entschei-dungen zum Zeitpunkt des Notfalls in-nerhalb von Sekunden oder Minuten fal-len, insbesondere im auserklinischen Be-reich aufgrund von begrenzten Informati-onen. Daher ist es wichtig, dass professio-nelle Helfer sich mit den zugrunde liegen-den Prinzipien vertraut machen, bevor sie in eine Situation geraten, in der eine Re-animationsentscheidung getroffen wer-den muss. Entscheidungen zum Lebens-ende und ethische Erwagungen sollen von professionellen Helfern also im Vorhinein und im jeweiligen gesellschaftlichen Kon-text erfolgen. Obwohl es nur wenige wis-senschaftliche Grundlagen gibt, die Anlei-tungen fur Entscheidungen am Lebensen-de bieten konnten, handelt es sich um ein wichtiges Thema. Daher wurden Informa-tionen fur professionelle Helfer in diese Re-animationsleitlinien aufgenommen.Diese Sektion der Leitlinien beschaf-tigt sich mit einigen wiederkehrenden ethischen Aspekten und Entscheidungen am Lebensende:F Ethische Grundprinzipien,F plotzlicher Kreislaufstillstand aus glo-baler Sicht,F Outcome und Prognosestellung,F wann Wiederbelebungsversuche be-ginnen und wann beenden,F Patientenverfugungen und Anwei-sungen zum „do not attempt resusci-tation“ (DNAR, d. h. kein Reanimati-onsversuch),F Anwesenheit von Familienangehori-gen wahrend der Reanimation,F Organbeschaffung,F Reanimationsforschung und infor-mierte Einwilligung sowieF Forschung und Ausbildung an gerade Verstorbenen.

Acute effects of combined high-frequency oscillation and tracheal gas insufflation in severe acute respiratory distress syndrome.

Objective:In acute respiratory distress syndrome (ARDS), high-frequency oscillation (HFO) improves oxygenation relative to conventional mechanical ventilation (CMV). Alveolar ventilation is improved by adding tracheal gas insufflation (TGI) to CMV. We hypothesized that combined HFO and TGI (HFO-TGI) might result in improved gas exchange relative to both standard HFO and CMV according to the ARDS Network protocol. Design:Prospective, randomized, crossover study. Setting:A 30-bed university intensive care unit. Patients:A total of 14 patients with early (<72 hrs in duration), severe (Pao2/Fio2 of <150 mm Hg and prerecruitment oxygenation index of 22.8 ± 1.9 [mean ± sem]), primary ARDS. Interventions:Patients were ventilated with HFO without (60 mins) and combined with TGI (6.1 ± 0.1 L/min, 60 mins) in random order. HFO sessions were repeated in inverse order within 24 hrs. HFO sessions were preceded and followed by ARDS Network CMV. Four recruitment maneuvers were performed during the study period. During HFO sessions, mean airway pressure was set at 1 cm H2O above the point of maximal curvature of the respiratory system expiratory pressure–volume curve. Measurements and Main Results:Gas exchange and hemodynamics were determined before, during, and after HFO sessions. HFO-TGI improved Pao2/Fio2 relative to HFO and CMV (174.5 ± 10.4 vs. 136.0 ± 10.0 and 105.0 ± 3.7 mm Hg, respectively, p < .05 for both) and oxygenation index relative to HFO (17.1 ± 1.3 vs. 22.3 ± 1.7, respectively p < .05). Pao2/Fio2 returned to baseline within 3 hrs after HFO. During HFO-TGI, shunt fraction and mixed venous oxygen saturation improved relative to CMV (0.36 ± 0.01 vs. 0.45 ± 0.01 and 77.8% ± 1.2% vs. 71.8% ± 1.3%, respectively, p < .05 for both). Paco2 and hemodynamics were unaffected by HFO sessions. Respiratory mechanics remained unchanged throughout the study period. Conclusions:In early onset, primary, severe ARDS, short-term HFO-TGI improves oxygenation relative to standard HFO and ARDS Network CMV.

The effects of nebulized salbutamol, external positive end- expiratory pressure, and their combination on respiratory mechanics, hemodynamics, and gas exchange in mechanically ventilated chronic obstructive pulmonary disease patients

We hypothesized that combined salbutamol and external positive end-expiratory pressure (PEEPe) may present additive benefits in chronic obstructive pulmonary disease (COPD) exacerbation. In 10 anesthetized, mechanically ventilated, and bronchodilator-responsive COPD patients exhibiting moderate intrinsic PEEP (PEEPi), we assessed respiratory system (rs) mechanics, hemodynamics, and gas exchange at (a) baseline (zero PEEPe [ZEEPe]), (b) 30 min after 5 mg of nebulized salbutamol administration (ZEEPe-S), (c) 30 min after setting PEEPe at baseline PEEPi level (PEEPe), and (d) 30 min after 5 mg of nebulized salbutamol administration with PEEPe maintained unchanged (PEEPe-S). Return of determined variable values to baseline values was confirmed before PEEPe application. Relative to ZEEPe, (a) at ZEEP-S, PEEPi (4.8 ± 0.7 versus 7.0 ± 1.1 cm H2O), functional residual capacity change (115.6 ± 23.1 versus 202.1 ± 46.0 mL), minimal rs (airway) resistance (9.3 ± 1.4 versus 11.8 ± 2.2 cm H2O·L−1·s−1), and additional rs resistance (5.2 ± 1.4 versus 7.2 ± 1.3 cm H2O·L−1·s−1) were reduced (P < 0.01), and hemodynamics were improved; (b) at PEEPe, PEEPi (3.7 ± 1.3 cm H2O) was reduced (P < 0.01), and gas exchange was improved; and (c) at PEEPe-S, PEEPi (2.0 ± 1.2 cm H2O) was minimized, and rs mechanics (static rs elastance included), hemodynamics, and gas exchange were improved. Conclusively, in carefully preselected COPD patients, bronchodilation/PEEPe exhibits additive benefits.

Acute postoperative pulmonary thromboembolism as a result of intravascular migration of a pigtail ureteral stent.

IMPLICATIONS The symptomatic obstruction of a pulmonary arterial branch secondary to the intravascular migration of a pigtail ureteral stent is reported. This iatrogenic complication may cause dyspnea, chest pain, or both after uneventful urologic procedures involving ureteral stents.

Intermittent recruitment with high-frequency oscillation/tracheal gas insufflation in acute respiratory distress syndrome

In acute respiratory distress syndrome (ARDS), recruitment sessions of high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) with short-lasting recruitment manoeuvres (RMs) may improve oxygenation and enable reduction of subsequent conventional mechanical ventilation (CMV) pressures. We determined the effect of adding HFO-TGI sessions to lung-protective CMV on early/severe ARDS outcome. We conducted a prospective clinical trial, subdivided into a first single-centre period and a second two-centre period. We enrolled 125 (first period, n=54) patients with arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) of <150 mmHg for >12 consecutive hours at an end-expiratory pressure of ≥8 cmH2O. Patients were randomly assigned to an HFO-TGI group (receiving HFO-TGI sessions with RMs, interspersed with lung-protective CMV; n=61) or CMV group (receiving lung-protective CMV and RMs; n=64). The primary outcome was survival to hospital discharge. Pre-enrolment ventilation duration was variable. During days 1–10 post-randomisation, Pa,O2/FI,O2, oxygenation index, plateau pressure and respiratory compliance were improved in the HFO-TGI group versus the CMV group (p<0.001 for group×time). Within days 1–60, the HFO-TGI group had more ventilator-free days versus the CMV group (median (interquartile range) 31.0 (0.0–42.0) versus 0.0 (0.0–23.0) days; p<0.001), and more days without respiratory, circulatory, renal, coagulation and liver failure (p≤0.003). Survival to hospital discharge was higher in the HFO-TGI group versus the CMV group (38 (62.3%) out of 61 versus 23 (35.9%) out of 64 subjects; p=0.004). Intermittent recruitment with HFO-TGI and RMs may improve survival in early/severe ARDS.

Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: A lethal cause of pneumonia in an adult immunocompetent patient

Necrotizing pneumonia and fatal septic shock were caused by Panton-Valentine leukocidin-positive, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) in a previously healthy, 61-y-old female. This patient did not belong to any high-risk group (e.g. homosexuals, military recruits, sports team members, etc.). CA-MRSA infection should be suspected in any adult with severe pneumonia/sepsis.