For over 20 years, Constantine Manthous, MD, has taught, researched, and practiced in the intensive care unit. His research has addressed a panoply of practical problems with a focus on weaning from mechanical ventilation and end-of-life ethics.
A few weeks ago, I contacted several PCCM fellowship directors to ask that they encourage fellows to share teaching conferences and points-of-view on the ATS blog. I received no response from two directors but a third was eager to engage.
For the record, this PD is a great talent. He is a nation-leading educator, scientist and – by all accounts -an excellent clinician. I’ll distill and paraphrase his response: fellows only have 3 years to get a huge amount accomplished. It would be a disservice to encourage them to produce content for the blog, deflecting their limited time/attention away from their once-in-a-lifetime opportunity to build the foundation of an academic career. Incisive on first glance.
We on the two coasts of the U.S. were thumped last week by what is sure to be the ugliest national election of our life-time. Politicians will perform “autopsies” to examine how/why a great country has chosen a President whose behavior throughout the election was decidedly (probably purposely) un-presidential. Aside from the extraordinary intuitions and showmanship of this modern PT Barnum, there may be interesting and relevant parallels in Medicine.
Recently, in the bayside village of Niantic on the eastern coast of Connecticut, I dined al fresco with two chief nurses from my old ICU. As the sun set over Long Island Sound, we caught up on families, fallen comrades, and lamented the perturbations of our professions.
It’s no coincidence that the AnnalsATSBlog launched with a focus on weaning. I spent most of my academic career studying methods to more rapidly liberate patients in acute respiratory failure from invasive mechanical ventilation.
Over many years in a previous position, I had the privilege of crafting a culture at Bridgeport Hospital in Connecticut that rapidly embraced new developments in the management of acute respiratory failure, including least sedation and daily spontaneous breathing trials (SBTs), sometimes years before confirmatory data arrived.
I hope readers will weigh in; this blog will be aimed to provoke discussion.
Blog#1: Opiates and us
Two years ago I “landed” in Niantic/New London, where I grew up, to practice 7 days of critical care and 12 days of primary care each month in a non-academic setting. After 20 years of academics, teaching and research, my wife and friends were sure it would be a bad move. But it’s been great fun and revelatory. I am likely among the few (oxymoronic) primary care intensivists in the country, and was struck immediately by the frequency of patients on prescription opiates and benzodiazepines. I’d served in some awfully tough cities (Hartford, south Chicago, Bridgeport) but the dimensions of substance, and especially opiate, abuse were staggering. Colleagues from other academic, big-city settings agree the problem in Southeast CT dwarfs our previous gigs.
Then came a spate of tragic heroin – or more exactly fentanyl-laced – overdose cases in New London. One rotation in a 48 hour period I had two 40’ish year olds brought in mostly brain dead. While complex social and economic convulsions certainly contributed to increasing opiate abuse nationally, and more so in New London county, some healthcare experts have offered a more reflective synthesis. In the 1990’s the medical establishment and laypress chastised physicians for treating pain insufficiently. “Patients won’t become addicted,” we were assured. And “pain is the 5th vital sign,” bone fide and required by hospital accreditors. Landmark articles in JAMA trumpeted the gross under-treatment of pain in patients with cancer and AIDS. As recently as 2005, Jane Brody wrote an article in The New Times entitled “When It Comes to Severe Pain, Doctors Still Have Much to Learn.” An “expert” was quoted: “Fear and lack of knowledge of these drugs prevent many doctors from prescribing them for people whose pain is caused by anything other than cancer.” And (eye-candy) PHARMA reps sold us on the safety of prescription opiates as they filled their coffers at the expense of society.
As a result, physicians, nurses and hospitals embraced this concept and, over a relatively brief span of 10 years, opiates were increasingly used first (rather than last) to treat all manner of pain, for indefinite periods. (The floodgates similarly opened for benzos as intensivists were brain-washed to use enormous doses that unarguably harmed patients.) Clinicians with no formal training in pain management were left to fathom when it was reasonable to stop opiates. When patients continued to complain of pain and/or had become increasingly tolerant or addicted to opiates they were left in a conundrum: how to withdraw them? Withdrawal can be a life-threatening process and very few clinicians know how. Meanwhile patients began to learn that they could obtain much more potent opiates at relatively low prices, illegally in the form of heroin. Our Governor Malloy acknowledged the problem and began to clamp down on opiate prescriptions starting January 1, 2016. But with so many patients now addicted, and so few addiction specialists, it is not clear that once cut off from prescriptions, these patients won’t, in desperation, seek heroin.
In our rush to compassionate care, we clinicians contributed to this problem. As a new primary care physician, I am struck by the number of patients – many in their 70’s and 80’s – who are habituated to opiates. One 80 year old admitted recently: “You can’t stop my oxycodone; I’m an addict,” she said half-jokingly. But it is the current fate of too many of our neighbors; and threatens too many of our children.
While the President, congressmen and governors have focused greater attention on this now- unavoidable problem, it needs to be a call to arms for physicians, patients and policy-makers. No single remedy is likely to fix this problem but consider:
While doctors, nurses and physician assistants are being trained, we will never have enough pain and withdrawal experts to catch up with this problem. We must all agree to write new prescriptions for opiates for only very limited periods, informing patients when to expect no more. For those who truly have chronic refractory pain, primary care physicians need to work with pain specialists to apply all other modalities (e.g. pain patches, gels, non-steroidal medications, pain-modulating medications, physical therapy, electrical stimulation, anesthetic injections, etc.) with a goal of reducing or eliminating opiates.
Patients who are already addicted must be convinced that only a small fraction of chronic pain patients truly need opiates forever; that opiates are a dead-end, appropriate for those who are dying, but harmful for all but a very few who wish to live fruitful lives.
While we cannot all become withdrawal experts, there are new FDA-approved medications for withdrawing opiate addicts – whether heroin or prescription opiates. Each primary care provider, nay every physician who contributed to the epidemic, might consider taking the 4-8 hour courses to be licensed to administer these medications. If each of us aimed to withdraw all the patients we currently have who don’t need opiates, and a handful of others, we’d go a long way to addressing this problem.
The Obama administration has earmarked $94 million to fortify opiate withdrawal programs in community health centers. But what about the multitude of non-indigent patients who are hooked, stranded, on opiates? The Market contributed to this problem and is a powerful mechanism to match supply and demand. If sufficient government monies are used to pay physicians to provide withdrawal services – i.e. a fair rate of reimbursement commensurate with the magnitude of the problem – clinicians will come. We need specific, well-remunerated codes for managing opiate withdrawal to draw more clinicians into the solution.
We physicians inadvertently contributed to the opiate crisis – with all good intentions – and now can become part of the solution. Else too many or our neighbors will suffer, enslaved by an epidemic of Medicine’s creation. Too many of our children will fall into this abyss until we own the problem.
A 55 year old man with a prior history of coronary disease and COPD has been intubated for 6 days after successful management of uroseptic shock. He is 8 liters net positive fluid balance, has stable vitals (maximal temperature is 101⁰), and is fully awake on sedation vacation. His ventilator settings are AC/12/500/50/5 and his ABG is 7.44/36/98. Your approach to medical and ventilator management (all the way to a trial of extubation) would include:
All of us in the ICU have learned that the “backend” of critical illness in the ICU is often more complicated than it looks. At face value, this patient who has been on the ventilator for about a week and who is now on low vent settings, would appear possibly ready for extubation. But there’s likely more to his story.
In order to maximize his safety and reduce his suffering, I would take a systematic and evidence-based approach currently endorsed by the SCCM in the ongoing ICU Liberation collaborative (www.iculiberation.org) by which to implement the PAD guidelines: the ABCDEF Bundle.
A. Assessment and management of pain. I would ask the nurse to tell me what his objective pain scale status is, hoping to hear that his CPOT is 0 to 2. If it was higher than that I would ask what the source of his pain was and try to use non-pharmacological management or non-opioid management if possible but also be generous with opioids if required (cognizant of the dangers of respiratory suppression in this patient with COPD and CHF).
B. Both SAT and SBT. This part is where excellent teamwork has to come into play between nurses and respiratory therapists. Since he is already awake and alert, he has passed the SAT and will appear ready for his SBT trial. I would listen for wheezes and a gallop to assess relevant organ dysfunction. Then I would put him on CPAP without pressure support and watch him for a couple of minutes and calculate his F/VT by squaring his respiratory rate and dividing by the minute ventilation (this is an identical calculation to f/Vt, but is a trick Al Baker and I developed when we were fellows doing our 1996 NEJM RCT so that we wouldn’t have to get perplexed about the best breath/Vt since the minute ventilation averages over multiple breaths.
If the calculation shows the patient to be breathing with the ratio way less than 100 (eg, 40–60), then we expect success. If his ratio is way over 100 (e.g. 140–160) we are likely headed for trouble.
Either way, we keep watching him and if no problems ensue, he would qualify for extubation after two hours of spontaneous breathing. We only use 30 minutes for patients who are straight forward without comorbidities, unlike this patient. If he does fail the SBT, I would likely push to extubate him to BiPAP with diuretics and nebs if he is wheezing. Prior to extubation I might check a “white card test” (Manthous) and a leak test.
C. Choice of drugs. Here our team would emphasize avoidance of sedation and the patient high risk for problems with post extubation failure and a thorough review of his entire medication regimen. I would also work to negate his 8 L volume excess.
D. Delirium assessment and management. We have shown that upwards of 1 in 3 alert ventilated ICU patients manifest ongoing brain dysfunction in the way of delirium. Because this problem is a risk factor for higher mortality, longer lengths of stay, cost, and long-term cognitive impairment, it is imperative that we check the patient for Delirium. We are told he is alert so we will assume RASS 0, but this is not enough information. In keeping with the PAD guidelines, we need data from either a CAM-ICU or ICDSC. Is he attentive or inattentive?
If our patient is inattentive, I would run through the mnemonic and Dr. DRE with the team. Diseases, Drug Removal, Environment. Does he have any nosocomial infections, ongoing COPD or CHF exacerbation symptoms, or even metabolic problems that could be causing delirium? Working with the Pharm.D and others on the team, I would want to make sure we stopped any deliriogenic drugs. Considering environmental causes, I would emphasize the use of eyeglasses, hearing aids, lights on during the day and off at night, other non-pharmacologic sleep aids, and of course aggressive mobility both because this is an intervention having been shown to reduce delirium and so that he will sleep better. All of this, if you noticed, is done before you ever consider adding a drug to treat the delirium. Antipsychotics are currently under investigation and an NIH-sponsored, three arm, placebo-controlled clinical trial.
E. Early mobility. Assess the patient’s pre-ICU mobility status. If the patient had been ambulatory, then mobilizing this patient is important regardless of whether or not he is extubated today. The team, whether it is a nurse or physician or physical therapist or occupational therapist, must prioritize maximizing his mobility hopefully to the point of ambulating down the hall, but starting even with standing up at the bedside and progressing from there. Remember, those bones were made for walking! When the patient says to me, “Dr. Ely, Guess what? I was out of the bed for 3 hour today.” I reply, “Yeah, well, guess what, that means you were IN the bed 21 hours. Let’s fix that.”
F. Family involvement and empowerment. This may seem obvious but remember to teach the family all about this ABCDEF bundle so that they will help keep us accountable for optimizing their loved ones safety and comfort. In addition, remind yourself that the relationship your patient has with his family is the most important one and that the family can do more for them than we ever will.
Note: this entire bundle can be run through in a matter of 30 – 60 seconds by an organized nurse and inter-professional team. Each of the components of the bundle is inextricably linked and tied to the other piece of the bundle and inappropriate conversation about the nurse’s report will usually lead to a fairly comprehensive discussion of the most important medical issues with that given patient. I would also address when I consider “soft underbellies” in the ICU (vulnerable points). That’s we always discuss nutrition/diet, ability to safely swallow post extubation, patients end-of-life preferences such as code status, and PUD and DVT prophylaxis.
Since this patient has been on the ventilator for multiple days and septic, and probably had delirium, he would qualify for our post I see you clinic. The patient will be discharged to whatever was the most appropriate location after his hospital ward stay and then would come back to our Friday ICU clinic where he will be seen by a nurse practitioner, neuropsychologist, pharmacist, and physician. From there, we would quarterback his needs and help him during his post ICU recovery to avoid ongoing problems from the post intensive care syndrome (PICS).
My management would be based on simple principles.
Our role in the ICU is 1) to treat the disease causing life threatening organ dysfunction (here antibiotics, and possible uro-drainage), 2) support organ function (here fluids, probably vasopressors, mechanical ventilation), 3) avoid or minimize the side effects of our therapies (here fluid retention, mechanical ventilation and intubation, sedation, bed rest), which includes removing these therapies as soon as possible.
I use these simple principles and try to base my individual approach on lessons learned from clinical research.
This patient seems to successfully survive the active phase of sepsis, be off sedation and awake. The next obvious action is to try to remove the ventilator. From the vignette, he has several items on a list that could make weaning complicated: history of COPD and coronary disease, fluid overload, and -if I understand correctly (I would ask the resident to avoid any ambiguity in his/her presentation)- FiO2 is 50%, which makes the PaO2/FiO2 ratio still below 200 mmHg. In the interpretation of this low oxygenation, I would like to know the trajectory of his lung function in the ICU and also his baseline, pre-ICU, lung function (is he on home oxygen therapy?). Importantly I would not however presuppose that weaning will be difficult and would test patient’s ability to be separated from the ventilator. Because my pre-test probability would be close to 50/50 I would be interested to have a first screening assessment measuring the rapid shallow breathing index either with a Wright spirometer on a T-piece or on CPAP0 PS0 on the ventilator (can be done everywhere at anytime) for about 3 minutes. If the index is below 100 breaths/min/L, I would proceed to a weaning test, also referred to a spontaneous breathing trial and would favor a T-piece (best technique to mimick extubation. See Straus et al AJRCCM 1998). In some case I would do a CPAP0 PS0 trial (which usually delivers 3 cm H20 of PS on modern ventilators) as equivalent to a T-piece. I would not decide to extubate for such a patient (see my pre-test probability) based on any other approach (see Thille et al AJRCCM 2013).
I this patient is doing really fine on the test I would proceed to extubation provided there is no sign of ischemia on ECG at the end of the trial. I would sample an ABG before extubation to guide my therapy: I would consider this patient at risk for extubation failure (COPD, hypoxemia). Before extubation I would decide to switch to high-flow oxygen therapy if the patient is hypoxemic (see Maggiore et al AJRCCM 2014) or to noninvasive ventilation if he is hypercapnic and acidotic (Thille et al see above). In both cases this would be used as a preventive treatment decided before extubation. If the patient deteriorates after extubation I would recommend reintubation without delay.
If the patient is doing poorly, I would try to understand why, and I would first suspect that fluid overload is a major contributor. A measurement of BNP or NTproBNP may reinforce this suspicion and may help to determine the dose of furosemide needed (see Mekontso Dessap et al AJRCCM 2012). I would also look at renal function because it may artificially increase BNP levels but also because it may require higher doses of furosemide in case of renal dysfunction. Note that furosemide does not improve renal function, it just helps with fluid management. If furosemide is given I would watch carefully electrolytes (K and bicar) and potentially add acetazolamide to avoid adding metabolic alkalemia to the picture. There may be an ischemic component (ECG during the trial) that may require additional treatment. Age, coronary disease, COPD may also all favor diastolic dysfunction (evidence of tachycardia, hypertension and desaturation during the trial), requiring vasodilators. At this stage (difficult weaning) an echocardiographic assessment of cardiac function may be useful to guide a cardiac medical therapy.
In such a case I would ventilate the patient in pressure support ventilation, or use a proportional mode (if clinicians are comfortable) such as proportional assist ventilation or neurally adjusted ventilatory assist and repeat the weaning test daily. I would consider other factors which may impede weaning such as delirium (see Mekontso Dessap Chest 2015), or muscle weakness. I may consider to have an ultrasound examination of his diaphragm as a cause of weaning failure (see Matamis et al ICM 2013). If the patient is repeatedly failing, trying to normalize work of breathing in this patient as early as possible may be very important. Pressure support is an easy mode to use with some caveats. Do not under-assist (pronounced use of accessory muscles) but also do not over-assist the patient, this may impair sleep (see Pathasarathy et al AJRCCM 2002) and this may be detected by the presence of ineffective efforts (see Thille et al ICM 2006). Proportional modes offer clear advantages in this regard.
My approach to patient management is based on simple steps.
It seems that the patients has done well and that a spontaneous breathing trial (SBT) can be performed. I assume that P/F ratio is > 200. The patient suffers COPD and we do not know his baseline gas exchange. It is possible that a P/F >170 or > 180 would suffice for the patient to tolerate an SBT. In patients with advanced COPD disease it is not reasonable to require a P/F ratio > 200. There is no evidence in these patients that 200 as opposed to 180 is associated with a greater SBT success.
The use of predictive indices is not warranted. None is associated with negative or positive predictive values higher than 80% in repeated studies. We should not forego an SBT if classical criteria (Chest 2001;120:375S) are met, and to let the patient prove his ability to breathe spontaneously and eventually be extubated. If classical criteria are met, I think the patient should undergo an SBT.
Even though there is no good level of evidence, I think we should discontinue sedation 18-24 h before the test. The fact that the patient cooperates at the time of the SBT does not guarantee that later on the patient may become somnolent after extubation due to still high sedation levels.
SBT can last only 30 min before extubation or re-connection to the ventilator. During the duration of the trial, a team member should watch the patient to assess the causes of failure of the SBT. Information obtained during that time is necessary if the patient fails, to plan treatments such as negative fluid balance, bronchodilators, etc., during the following 24 h before a new attempt is planned.
My proposal is to use T piece or PSV 2 cm H20 for the SBT. After 6 days of intubation, the upper airway after extubation can be shaped by the endotracheal tube. Thus the patient is going to face a situation after extubation similar to that during T piece breathing (Strauss et a., AJRCCM 1998).
A cuff leak test helps predict upper airway difficulties after extubation. If the test is negative (leak > 100-150 ml) the patient should be extubated. If the test is positive (no leak) the extubation can be postponed for 24 h. During this time, the administration of corticosteroids (methilprednisolone 40 mg q 6H; see Crit Care Med 2006;343:1345 and Crit Care 2007;11:R72) could reduce the obstruction. In any case, patients with a positive cuff leak test should be extubated during morning hours, and with personnel and material ready for a difficult intubation.
Reasons for SBT failure are many. In the present case, the most likely reasons are ventricular failure and clinically obvious muscle weakness. In the first case, after re-connection to the ventilator we can plan a negative balance of 1000 ml before repeating the SBT. In the case of muscle weakness, re-connection to the ventilator and a repeat SBT each 24 hours, is the most reasonable option. When the patient tolerates the SBT, extubation should be carried out. Re-intubation rate in these patients is 30-40%. Despite this risk, we should not negate the option to the 60-70% of patients who will succeed.
If there is respiratory failure after extubation, NIV could be used, monitoring the response during the first hours (PaO2, high respiratory rate, high heart rate, lack of cooperation). If there is no improvement the patient should be re-intubated promptly, as delay in intubation increases the risk of death and delays recovery before a new SBT can be attempted.