The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

Background
This is an update of a review last published in Issue 5, 2010, of The Cochrane Library. Reducing weaning time is desirable in minimizing potential complications from mechanical ventilation. Standardized weaning protocols are purported to reduce time spent on mechanical ventilation. However, evidence supporting their use in clinical practice is inconsistent.

Objectives
The first objective of this review was to compare the total duration of mechanical ventilation of critically ill adults who were weaned using protocols versus usual (non-protocolized) practice.

The second objective was to ascertain differences between protocolized and non-protocolized weaning in outcomes measuring weaning duration, harm (adverse events) and resource use (intensive care unit (ICU) and hospital length of stay, cost).

The third objective was to explore, using subgroup analyses, variations in outcomes by type of ICU, type of protocol and approach to delivering the protocol (professional-led or computer-driven).

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2014), MEDLINE (1950 to January 2014), EMBASE (1988 to January 2014), CINAHL (1937 to January 2014), LILACS (1982 to January 2014),  ISI Web of Science and ISI Conference Proceedings (1970 to February 2014), and reference lists of articles. We did not apply language restrictions. The original search was performed in January 2010 and updated in January 2014.

Selection criteria
We included randomized controlled trials (RCTs) and quasi-RCTs of protocolized weaning versus non-protocolized weaning from mechanical ventilation in critically ill adults.

Data collection and analysis
Two authors independently assessed trial quality and extracted data. We performed a priori subgroup and sensitivity analyses. We contacted study authors for additional information.

Main results
We included 17 trials (with 2434 patients) in this updated review. The original review included 11 trials. The total geometric mean duration of mechanical ventilation in the protocolized weaning group was on average reduced by 26% compared with the usual care group (N = 14 trials, 95% confidence interval (CI) 13% to 37%, P = 0.0002). Reductions were most likely to occur in medical, surgical and mixed ICUs, but not in neurosurgical ICUs. Weaning duration was reduced by 70% (N = 8 trials, 95% CI 27% to 88%, P = 0.009); and ICU length of stay by 11% (N = 9 trials, 95% CI 3% to 19%, P = 0.01). There was significant heterogeneity among studies for total duration of mechanical ventilation (I2 = 67%, P < 0.0001) and weaning duration (I2 = 97%, P < 0.00001), which could not be explained by subgroup analyses based on type of unit or type of approach.

Authors' conclusions
There is evidence of reduced duration of mechanical ventilation, weaning duration and ICU length of stay with use of standardized weaning protocols. Reductions are most likely to occur in medical, surgical and mixed ICUs, but not in neurosurgical ICUs. However, significant heterogeneity among studies indicates caution in generalizing results. Some study authors suggest that organizational context may influence outcomes, however these factors were not considered in all included studies and could not be evaluated. Future trials should consider an evaluation of the process of intervention delivery to distinguish between intervention and implementation effects. There is an important need for further development and research in the neurosurgical population.

/pdf/protocolized-versus-non-protocolized-weaning-for-reducing-3ae7xtxty6.pdf

Protocolized versus non‐protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients

Objectives:Cardiac surgery, including coronary artery bypass, cardiac valve, and aortic procedures, is among the most common surgical procedures performed in the United States. Successful outcomes after cardiac surgery depend on optimum postoperative critical care. The cardiac intensivist must have

Postoperative Critical Care of the Adult Cardiac Surgical Patient. Part I: Routine Postoperative Care

BACKGROUND\nReducing weaning time is desirable in minimizing potential complications from mechanical ventilation. Standardized weaning protocols are purported to reduce time spent on mechanical ventilation. However, evidence supporting their use in clinical practice is inconsistent.\n\n\nOBJECTIVES\nTo assess the effects of protocolized weaning from mechanical ventilation on the total duration of mechanical ventilation for critically ill adults; ascertain differences between protocolized and non-protocolized weaning in terms of mortality, adverse events, quality of life, weaning duration, intensive care unit (ICU) and hospital length of stay (LOS); and explore variation in outcomes by type of ICU, type of protocol and approach to delivering the protocol.\n\n\nSEARCH STRATEGY\nWe searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2010), MEDLINE (1950 to 2010), EMBASE (1988 to 2010), CINAHL (1937 to 2010), LILACS (1982 to 2010), ISI Web of Science and ISI Conference Proceedings (1970 to 2010), Cambridge Scientific Abstracts (inception to 2010) and reference lists of articles. We did not apply language restrictions.\n\n\nSELECTION CRITERIA\nWe included randomized and quasi-randomized controlled trials of protocolized weaning versus non-protocolized weaning from mechanical ventilation in critically ill adults.\n\n\nDATA COLLECTION AND ANALYSIS\nThree authors independently assessed trial quality and extracted data. A priori subgroup and sensitivity analyses were performed. We contacted study authors for additional information.\n\n\nMAIN RESULTS\nEleven trials that included 1971 patients met the inclusion criteria. The total duration of mechanical ventilation geometric mean in the protocolized weaning group was on average reduced by 25% compared with the usual care group (N = 10 trials, 95% CI 9% to 39%, P = 0.006); weaning duration was reduced by 78% (N = 6 trials, 95% CI 31% to 93%, P = 0.009); and ICU LOS by 10% (N = 8 trials, 95% CI 2% to 19%, P = 0.02). There was significant heterogeneity among studies for total duration of mechanical ventilation (I(2) = 76%, P < 0.01) and weaning duration (I(2) = 97%, P < 0.01), which could not be explained by subgroup analyses based on type of unit or type of approach.\n\n\nAUTHORS' CONCLUSIONS\nThere is some evidence of a reduction in the duration of mechanical ventilation, weaning duration and ICU LOS with use of standardized protocols, but there is significant heterogeneity among studies and an insufficient number of studies to investigate the source of this heterogeneity. Although some study authors suggest that organizational context may influence outcomes, these factors were not considered in all included studies and therefore could not be evaluated.

/pdf/protocolized-versus-non-protocolized-weaning-for-reducing-2riervsesu.pdf

Protocolized versus non-protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients (Review)

Mechanical ventilation (MV) is an essential part of modern intensive care medicine. MV is performed in patients with severe respiratory failure caused by insufficiency of respiratory muscles and/or lung parenchymal disease when/after other treatments, (i. e. medication, oxygen, secretion management, continuous positive airway pressure or nasal highflow) have failed.MV is required to maintain gas exchange and to buy time for curative therapy of the underlying cause of respiratory failure. In the majority of patients weaning from MV is routine and causes no special problems. However, about 20 % of patients need ongoing MV despite resolution of the conditions which precipitated the need for MV. Approximately 40 - 50 % of time spent on MV is required to liberate the patient from the ventilator, a process called "weaning."There are numberous factors besides the acute respiratory failure that have an impact on duration and success rate of the weaning process such as age, comorbidities and conditions and complications acquired in the ICU. According to an international consensus conference "prolonged weaning" is defined as weaning process of patients who have failed at least three weaning attempts or require more than 7 days of weaning after the first spontaneous breathing trial (SBT). Prolonged weaning is a challenge, therefore, an inter- and multi-disciplinary approach is essential for a weaning success.In specialised weaning centers about 50 % of patients with initial weaning failure can be liberated from MV after prolonged weaning. However, heterogeneity of patients with prolonged weaning precludes direct comparisons of individual centers. Patients with persistant weaning failure either die during the weaning process or are discharged home or to a long term care facility with ongoing MV.Urged by the growing importance of prolonged weaning, this Sk2-guideline was first published in 2014 on the initiative of the German Respiratory Society (DGP) together with other scientific societies involved in prolonged weaning. Current research and study results, registry data and experience in daily practice made the revision of this guideline necessary.The following topics are dealt with in the guideline: Definitions, epidemiology, weaning categories, the underlying pathophysiology, prevention of prolonged weaning, treatment strategies in prolonged weaning, the weaning unit, discharge from hospital on MV and recommendations for end of life decisions.Special emphasis in the revision of the guideline was laid on the following topics:- A new classification of subgroups of patients in prolonged weaning- Important aspects of pneumological rehabilitation and neurorehabilitation in prolonged weaning- Infrastructure and process organization in the care of patients in prolonged weaning in the sense of a continuous treatment concept- Therapeutic goal change and communication with relativesAspects of pediatric weaning are given separately within the individual chapters.The main aim of the revised guideline is to summarize current evidence and also expert based- knowledge on the topic of "prolonged weaning" and, based on the evidence and the experience of experts, make recommendations with regard to "prolonged weaning" not only in the field of acute medicine but also for chronic critical care.Important addressees of this guideline are Intensivists, Pneumologists, Anesthesiologists, Internists, Cardiologists, Surgeons, Neurologists, Pediatricians, Geriatricians, Palliative care clinicians, Rehabilitation physicians, Nurses in intensive and chronic care, Physiotherapists, Respiratory therapists, Speech therapists, Medical service of health insurance and associated ventilator manufacturers.

[Prolonged weaning: S2k-guideline published by the German Respiratory Society].

Background: Adaptive support ventilation (ASV) is a microprocessor-controlled mode of mechanical ventilation that switches automatically from controlled ventilation to assisted ventilation and selects ventilatory settings according to measured lung mechanics. Methods: In a randomized controlled trial, non-fast-track coronary artery bypass grafting patients' lungs were ventilated with ASV or pressure-controlled/pressure-support ventilation (control) to compare time until tracheal extubation, duration of controlled ventilation versus assisted ventilation, and ventilation characteristics. Results: One hundred twenty-eight consecutive patients were randomized. ASV patients had their tracheas extubated after median 16.4 and interquartile range 12.5-20.8 hr, and control patients after 16.3 (13.7-19.3) hr, respectively (P = 0.97). The percentage of time patients were on assisted ventilation (expressed as the median percentage of total duration of ventilation) was 43% (28%-67%) in the ASV group and 52% (33%-75%) in the control group (P < 0.05). However, the number of switches from controlled to assisted ventilation was higher in the ASV group (43.0 [14.0-74.0]) than in the control group (4.0 [2.0-9.0]) (P < 0.001). In ASV patients, mean tidal volumes were significantly larger during controlled ventilation than in control patients (8.6 +/- 0.8 mL/kg predicted body weight vs 7.1 +/- 1.4 mL/kg predicted body weight; P = 0.05), and no differences in tidal volumes were found during assisted ventilation. Conclusion: Weaning automation with ASV is feasible and safe in non-fast-track coronary artery bypass grafting patients. Time until tracheal extubation with ASV equals time until tracheal extubation with standard weaning and allows for frequent (automatic) switches between controlled and assisted ventilation

Weaning automation with adaptive support ventilation: a randomized controlled trial in cardiothoracic surgery patients.

Background. Cardiac surgery-related pulmonary complications include alterations in lung mechanics and anomalies in gas exchange. Higher levels of positive end-expiratory pressure (PEEP) have been suggested to benefit cardiac surgical patients. We compared respiratory compliance, arterial oxygenation and time rill tracheal extubation in 2 cohorts of patients weaned from mechanical ventilation with different levels of PEEP after elective and uncomplicated coronary artery bypass grafting (CABG). We hypothesized that higher PEEP levels improve pulmonary compliance and gas exchange in the first hours of weaning from mechanical ventilation, but not to shorten time till tracheal extubation. Methods. Secondary retrospective analysis of 2 randomized controlled trials: in the first trial patients were weaned with PEEP levels of 10 cmH(2)O for the first 4 hours followed by PEEP levels of 5 cmH(2)O until tracheal extubation (high PEEP, HP); and the second trial patients were weaned with PEEP levels of 5 cmH(2)O during the entire weaning phase (low PEEP LP). The primary endpoint was pulmonary compliance. Secondary endpoints included arterial oxygenation, duration of mechanical ventilation and postoperative pulmonary complications. Results. The analysis included 121 patients; 60 HP patients and 61 LP patients. Baseline characteristics were similar. Compared to LP patients, HP patients had a better pulmonary compliance, 47.2 +/- 14.1 versus 42.7 +/- 10.2 ml/cmH(2)O (P <0.05), and higher levels PaO2, 18.5 +/- 6.6 (138.75 +/- 49.5) versus 16.7 +/- 5.4 (125.25 +/- 40.5) kPa (mmHg) (P <0.05). Patients in the HP group were less frequent in need of supplementary oxygen after ICU discharge. These differences remained present during the entire weaning phase, even after reduction of PEEP. However, HP patients had a longer time rill tracheal extubation, 16.9 +/- 6.1 versus 10.5 +/- 5.0 hours (P <0.001). HP patients had longer durations of postoperative infusion of propofol, 4.9 (2.6-7.4) versus 3.5 (1.8-5.8) hours (P <0.05). There were no differences in use of inotropes. Cummulative fluid balances were sligthly higher in HP patients. Conclusion. Use of higher PEEP levels after elective uncomplicated CABG improves pulmonary compliance and oxygenation but seems to be associated with a delay in tracheal extubation. (Minerva Anestesiol 2012;78:790-800)

Positive end-expiratory pressure following coronary artery bypass grafting

BACKGROUND: It is uncertain whether adaptive support ventilation (ASV) accelerates weaning of nonfast-track cardiothoracic surgery patients. A lower operator set %-minute ventilation with ASV may allow for an earlier definite switch from controlled to assisted ventilation, potentially hastening tracheal extubation. We hypothesized that ASV using protocolized de-escalation and escalation of operator set %-minute ventilation (ASV-DE) reduces time until tracheal extubation compared with ASV using a fixed operator set %-minute ventilation (standard ASV) in uncomplicated patients after nonfast-track coronary artery bypass graft. METHODS: We performed a randomized controlled trial comparing ASV-DE with standard ASV. With ASV-DE, as soon as body temperature was >35.0 degrees C with pH > 7.25, operator set %-minute ventilation was decreased stepwise to a minimum of 70%. RESULTS: Sixty-three patients were randomized to ASV-DE, and 63 patients to standard ASV. The duration of mechanical ventilation was not different between groups (10.8 [6.5-16.1] vs 10.7 [6.6-13.9] hours, ASV-DE versus standard ASV; P = 0.32). Time until the first assisted breathing period was shorter (3.1 [2.0-6.7] vs 3.9 [2.1-7.5] hours) and the number of assisted ventilation episodes was higher (78 [34-176] vs 57 [32-116] episodes), but differences did not reach statistical significance. The duration of assisted ventilation episodes that ended with tracheal extubation was different between groups (2.5 [0.9-4.6] vs 1.4 [0.3-3.5] hours, ASV-DE versus standard ASV; P <0.05). CONCLUSION: Compared with standard ASV, weaning of patients after nonfast-track coronary artery bypass graft using ASV with protocolized de-escalation and escalation does not shorten time to tracheal extubation. (Anesth Analg 2010;111:961-7)

Adaptive support ventilation with protocolized de-escalation and escalation does not accelerate tracheal extubation of patients after nonfast-track cardiothoracic surgery.

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Weaning automation with adaptive support ventilation: a randomized controlled trial in cardiothoracic surgery patients.

Positive end-expiratory pressure following coronary artery bypass grafting

Adaptive support ventilation with protocolized de-escalation and escalation does not accelerate tracheal extubation of patients after nonfast-track cardiothoracic surgery.