而对血流动力学不稳定、颅内压增高、急性出血、脊柱损伤、骨科手术、近期腹部手术、妊娠等不宜采用俯卧位通气。
作者：PEEPman
时间：2006-03-10 22:04:04
Mechanical ventilation in ARDS: One size does not fit all - Editorial AJCCM
Fri, 20 May 2005
ARMA was a government-sponsored, $41 million experiment involving 861 critically ill patients with severe lung injury--i.e., acute respiratory distress syndrome (ARDS). It has been at the center of continuing debate prompted by revelations that researchers at 14 of the nation's major medical research institutions comprising the ARDS Network,* violated fundamental medical ethics principles. [1] [2]
Patients with ARDS almost always need to be supported with mechanical ventilation to help them breathe. During this kind of support, breaths, termed tidal volumes, are administered to patients with a ventilator to inflate the lung to deliver oxygen and remove carbon dioxide from the blood.
However, lungs with ARDS are much stiffer than healthy lungs. In the 1980's emerging research strongly suggested that although necessary for survival, if tidal volumes with mechanical ventilation were too large, the high airway pressures they produced might themselves be harmful.
In 1992, a survey of more than 1,000 physicians caring for patients with ARDS showed that most were aware that tidal volumes producing increased airway pressures might be harmful and that physicians adjusted their practice to account for this. [3] A consensus conference of physicians in 1993 warned of the need to reduce tidal volumes if airway pressures were high, and recommended that physicians reduce tidal volumes when necessary to ensure that airway pressures remained below a potentially harmful level. [4]
NIH sponsored the ARMA study to investigate the benefits of reducing tidal volumes in ARDS patients. Between 1996 and 1999, the ARDS Network enrolled 861 patients out of an eligible pool of 3,448 patients. Patients who were enrolled in this experiment had been receiving
oxygen at a tidal volume setting according to the judgment of their primary, critical care physician. They were withdrawn from that ventilation setting, and randomized to receive one of two tidal volume settings--either high (12 ml/kg) which was termed \(6 ml/kg).
The experiment failed to include a comparison control group receiving the current best treatment--which included individualized ventilation settings determined by the condition of the individual patient's lungs.
Most of the patients enrolled in this randomized experiment were unable to Provide informed consent. Furthermore, the consent forms that had been approved by the institutional review boards (IRBs) at the participating hospitals ALL failed to comply with federal requirements of disclosure. See: [url]http://www.ahrp.org/ethical/CaromeARDS082802.php[/url]
In fact, none of the consent forms informed patients or their families that they would be withdrawn from current best therapeutic treatment and randomly assigned to a fixed ventilation setting which might increase their risk of dying. Neither were they informed that an alternative to participating in the experiment was available at the same medical center.
On July 29, 2002, AHRP filed a complaint with the federal Office of Human Research Protections about violations of informed consent. See: [url]http://www.ahrp.org/ethical/Koski0729.php[/url]
After enrolling more than 860 patients the study was stopped because mortality was substantially higher in the high tidal volume group (12ml/kg, 41%) compared to the low tidal volume group (6ml/kg, 31%). The ARDS investigators concluded that the low tidal volume (6ml/kg) increased survival rate and recommended that it should be applied to all patients with ARDS. [1]
Following publication of the trial in the New England Journal of Medicine, critical care physician-scientists at the NIH who analyzed the ARDS Network report raised concerns about the design of the experiment in the American Journal of Respiratory and Critical Care Medicine (AJRCCM). [5]
This independent analysis raised the following concerns about the design of the trial: First, airway pressures associated with the 12 mg/kg tidal volume were significantly higher than what critical care physicians were routinely administering in standard practice to their patients at the time of the trial. Second, the trials failed to include a control group in which patients would be provided individualized ventilation
settings--as is the practice in standard care, and is required under the Declaration of Helsinki ethical research standards. [6] Ethical research requires that:
\and therapeutic methods.\
Other groups of investigators were also examining what routine ventilatory care was both before and during the ARDS trial. These studies showed that physicians varied tidal volumes based on how injured or stiff the lungs of patients were. A very sick patient with a very stiff lung would get a low tidal volume while a patient with a more pliant lung would receive a higher tidal volume.
Randomizing patients to high or low tidal volumes without regard for their underlying level of lung injury was (and is) contrary to what was at the time--and continues to be--the best therapeutic method of care.
Therefore, the significant findings of the ARDS Network experiment may relate largely to having increased mortality in patients with very stiff lungs who had their tidal volumes increased to 12ml/kg.
Ultimately the ARDSNET trial is impossible to interpret and its recommendations that all patients with ARDS should get very low tidal volumes--should be rejected precisely because the trial failed to provide a randomly-selected control group of patients who received standard treatment.
\Charles Natanson and Peter Eichacker, in the current issue of the AJRCCM re-analyzes the ARDSNET data and additional data obtained via the Freedom of Information Act. [7]
The editorial analysis shows that \not enrolled in the trial (32%).
Deans, et al, examined data from patients before and after randomization. With enrollment in the trial, earlier routine care for patients was stopped. Analysis showed that in patients with stiff (sicker) lungs, increasing tidal volumes from routine care levels after randomization
increased mortality rates. Similarly, in patients with less injured, more elastic lungs, reducing tidal volumes from routine care also increased mortality
If lung stiffness and the resultant airway pressures dictated tidal volume selection by physicians routinely, then patients who were randomized to receive tidal volumes different from those their primary care physicians had prescribed were put in harm's way.
The lessons from the ARMA-ARDS Network experiment:
If the researchers had complied with ethical standards of informed consent and the Helsinki provision requiring that an experimental treatment must be tested against \needlessly. Furthermore, information might have been gained to benefit future patients as well.
But given the ARDS Network's disregard for the patients' human right to informed consent, and their flawed trial design, the $41 million ARMA experiment was an egregious mistrial which increased mortality.
A question arises about the ethical justification of randomization to a fixed dose treatment in research involving critically ill patients whose very life depends on sensitive adjustments to every aspect of their care and treatment from moment to moment.
Why should investigators be free to use procedures that increase the risk of death when the information they seek may be obtained using other research avenues?
Indeed, the second principle of the Nuremberg Code (1947) stipulates specifically that: \results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.\
Finally, the ARMA-ARDS experiment is an indictment of the IRB system and the bioethics community. IRBs at major medical research institutions that approved this experiment and others like it have demonstrated their incapacity to exercise their legal authority for the protection of human subjects. By approving experiments whose very design violated fundamental ethical principles and whose patient enrollment failed to comply with federal informed consent requirements, they share in the responsibility for the resulting preventable deaths.
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