Changes in exhaled 13CO2/12CO2 breath delta value as an early indicator of infection in intensive care unit patients

BACKGROUND We have developed a new, noninvasive predictive marker for onset of infection in surgical intensive care unit (ICU) patients. The exhaled 13CO2/12CO2 ratio, or breath delta value (BDV), has been shown to be an early marker for infection in a proof of concept human study and in animal models of bacterial peritonitis. In these studies, the BDV changes during onset and progression of infection, and these changes precede physiological changes associated with infection. Earlier diagnosis and treatment will significantly reduce morbidity, mortality, hospitalization costs, and length of stay. The objective of this prospective, observational, multicenter study was to determine the predictive value of the BDV as an early diagnostic marker of infection.

METHODS Critically ill adults after trauma or acute care surgery with an expected length of stay longer than 5 days were enrolled. The BDV was obtained every 4 hours for 7 days and correlated to clinical infection diagnosis, serum C-reactive protein, and procalcitonin levels. Clinical infection diagnosis was made by an independent endpoint committee. This trial was registered at the US National Institutes of Health ( NCT02327130.

RESULTS Groups were demographically similar (n = 20). Clinical infection diagnosis was confirmed on day 3.9 ± 0.63. Clinical suspicion of infection (defined by SIRS criteria and/or new antibiotic therapy) was on day 2.1 ± 0.5 in all infected patients. However, 5 (56%) of 9 noninfected subjects also met clinical suspicion criteria. The BDV significantly increased by 1‰ to 1.7‰ on day 2.1 after enrollment (p < 0.05) in subjects who developed infections, while it remained at baseline (± 0.5‰) for subjects without infections.

CONCLUSION A BDV greater than 1.4‰ accurately differentiates subjects who develop infections from those who do not and predicts the presence of infection up to 48 hours before clinical confirmation. The BDV may predict the onset of infection and aid in distinguishing SIRS from infection, which could prompt earlier diagnosis, earlier appropriate treatment, and improve outcomes.

LEVEL OF EVIDENCE Diagnostic test, level III.

Bacteria-Ridden Stethoscopes Abound in Hospitals

Stethoscopes used in an intensive care unit (ICU) are loaded with bacteria, including those that may be associated with hospital-acquired infections (HAIs), new data show. Moreover, standard cleaning methods did not eliminate the problems.

“Practitioner stethoscopes are contaminated by a plethora of bacteria, including organisms that may be associated with nosocomial infections. Cleaning reduces contamination but does not bring the bacterial biomass down to the level of clean stethoscopes nor does it significantly change the overall community composition. Thus, stethoscopes are a potential vector of HAI transfer,” the researchers write.

The study by Vincent R. Knecht, BS, from the Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues was published online December 12 in Infection Control and Hospital Epidemiology.

“It is well documented that practitioner stethoscopes are not routinely disinfected, and studies based on bacterial culture show that they may be contaminated with potential pathogens including methicillin-resistant and
-sensitive Staphylococcus spp, multidrug-resistant P. aeruginosa, Acinetobacter spp, Enterococcus spp, Escherichia coli, Klebsiella spp, and Streptococcus spp…. Culture-based studies are limited, however, because culture can only identify agents of a priori interest but not entire microbial communities that may be present,” the researchers explain.

Therefore, the researchers used bacterial 16S ribosomal RNA gene sequencing to gain “unbiased profiling of entire bacterial communities” present on stethoscopes used in a medical ICU.

In the first set of stethoscopes (set A), they tested 20 stethoscopes carried by practitioners (physicians, nurses, and respiratory therapists), 20 individual-use patient-room stethoscopes, and 20 clean unused individual-use stethoscopes. In a second set (set B), the researchers tested 10 practitioner stethoscopes that were sampled before and after standardized cleaning (wiping vigorously with a hydrogen peroxide wipe for 60 seconds and left to dry).

Set C contained an additional 20 practitioner stethoscopes that were sampled before and after cleaning by the practitioner using the practitioner’s usual method of cleaning. Practitioners used hydrogen peroxide wipes (n = 14), alcohol swabs (70% isopropyl alcohol; n = 3), or bleach wipes (n = 3) to clean their stethoscopes and followed their personal preference regarding duration of cleaning.

The researchers found that all stethoscopes used in the ICU were significantly contaminated with a variety of pathogens. The highest bacterial contamination levels were found on practitioner stethoscopes, followed by patient-room stethoscopes. Bacterial contamination levels on clean stethoscopes and background controls were indistinguishable from each other.

Table. Potential Nosocomial Pathogens on Practitioner Stethoscopes

Set A (n = 20) Set C (n = 20, before cleaning)
Organism Frequency, No. (%) Frequency, No. (%)
Staphylococcus spp 20 (100) 20 (100)
S aureus 11 (55) 13 (65)
Pseudomonas spp 16 (80) 20 (100)
Acinetobacter spp 13 (65) 20 (100)
Clostridium spp 8 (40) 12 (60)
Enterococcus spp 8 (40) 18 (90)
Stenotrophomonas spp 7 (35) 18 (90)
Burkholderia spp 3 (15) 3 (15)


Staphylococcus spp were present on all stethoscopes; the investigators were able to determine the species on some of those, and more than half were contaminated with Staphylococcus aureus, even after practitioner cleaning.

“Both cleaning methods resulted in a significant reduction in bacterial contamination regardless of cleaning method,” the authors write. “In the standardized cleaning group, 5 of 10 stethoscopes fell below the level of the clean stethoscopes…. In the practitioner-preferred cleaning group, 2 of 10 stethoscopes fell below the level of clean stethoscopes.”

“This study underscores the importance of adhering to rigorous infection control procedures, including fully adhering to CDC [Centers for Disease Control and Prevention]–recommended decontamination procedures between patients, or using single-patient-use stethoscopes kept in each patient’s room,” senior author Ronald Collman, MD, a professor of medicine and pulmonary, allergy and critical care at the University of Pennsylvania Perelman School of Medicine, Philadelphia, said in a news release.

Molecular analysis of bacterial contamination on stethoscopes in an intensive care unit



Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.


MethodsWe used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.


ResultsBacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.


ConclusionsStethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.

Each Patient Is a Unique Human Being, Not a Disease or a Group of Symptoms

Physician Louis P. Voigt is a specialist in critical care medicine and a member of Memorial Sloan Kettering’s Anesthesia and Critical Care Medicine Service.

In October, Dr. Voigt was the MSK winner of the 2014 MSK Wholeness of Life Award. This honor is presented annually by the HealthCare Chaplaincy Network to individuals “who demonstrate respect for human beings as whole persons” in their treatment of patients, families, and colleagues, and who practice medicine “with an appreciation for the interrelated functioning of body, mind, and spirit in illness and recovery.”

Dr. Voigt is a strong believer in the holistic approach to medicine that the Wholeness of Life Award celebrates, and shares his expertise through his roles as doctor, colleague, teacher, and mentor.

Here, he talks with us about his work and his commitment to his patients and their families.

Can you tell us a little about what you do in critical care medicine?

As a critical care medicine specialist with a background in internal medicine and pulmonary diseases, my work focuses on patients in our Intensive Care Unit (ICU) with life-threatening conditions who are in need of close monitoring and frequent interventions.

How did you come to do this work?

I believe it began early in life. I grew up in Haiti surrounded by family — four sisters and two loving parents — all of whom instilled in me a profound awareness of the importance and the need to serve others. In my crowded but caring home, I also learned the benefit of having someone nearby, if only as a witness to your experience — someone with whom to share a moment in time. So I think I have an understanding of the great value inherent in simply being present and available to another human being, especially during moments of suffering.

This is obviously particularly significant when it comes to working with patients and families in the ICU.

It absolutely is. Patients and families often feel overwhelmed in the ICU by the respirators and other life-support machines, the infusion pumps, the monitors, the wires, and the alarms. I’m committed to helping patients and their loved ones through this difficult and emotionally trying time.

Suffering is a process that is similar whether you’re a poor person in Haiti or a patient at MSK. It’s a contradictory process; moments of joy and laughter sometimes appear in the midst of pain. But for the person suffering, there is generally a sustained need for the presence of another human being. And I believe in treating emotional distress as a true emergency.

Can you elaborate a bit more on that?

Certainly. I think it’s vital to engage all the resources we have to help patients and families when they’re in crisis. So, for example, I ask our social workers to meet with families to “make a diagnosis” — and by that I mean to try to understand how a family is coping when their loved one is in the ICU and what their needs may be.

I also ask our nurses and therapists to develop treatment strategies for our patients that go beyond dealing with their physical symptoms; in other words, strategies to support the people they are beyond their particular illness. In our ICU, each patient is a unique human being, never just a disease or a group of symptoms.

Finally, I encourage our ICU nurse practitioners and my fellow doctors to spend as much time as they can in the unit so that they’re as available as possible to both our patients and their loved ones.

A colleague who nominated you for the Wholeness of Life Award said of you that you “empathize with patients and help them see the end-of-life journey with clarity and less fear.” In the ICU you and your colleagues are confronted with death. Can you talk about this?

Possibly most important to patients and their loved ones during this final, singular event is that I make myself available to them. So in meetings with patients and families, my first question always is, “How can I help you?” And I listen to their answers with an open mind and heart.

People reach their comfort zones with the prospect of death at different speeds — and that’s true for my professional colleagues as well as for patients and their families. Sometimes staff members have a hard time letting go of patients who have come to the end of their journey. You can’t ignore or minimize these emotions. Instead, you need to focus on what was achieved during that person’s time with us. And, in fact, on what is achieved every day at MSK.

Although I am a frequent witness to the end of life, I also need to say that there are numerous times when we see a patient turn a corner, respond to treatment, and leave the ICU. There are definitely happy endings, and there are many survivors.

Any other thoughts?

I think it’s important to remind ourselves that at the end of the day, we’re all finite. However, in my opinion, none of us is simply an accident of nature. We’re far too interesting and complex to be random. Indeed, my father was a professor and taught me to look deeper, to see beyond the obvious and the immediately knowable, to look for what’s hidden and, often, quite significant.

Albumin Supplementation in Sepsis Patients.

Fluid administration is one of the most common items managed every day in hospitalized and intensive care unit (ICU) patients. The optimal fluid for sepsis resuscitation remains unknown, with concerns about both crystalloids and colloids.[1]

Caironi and colleagues sought to examine whether albumin supplementation would benefit patients with severe sepsis and septic shock. This study randomly assigned 1818 of these patients within 24 hours of ICU admission to receive either crystalloids or crystalloids plus albumin supplementation, to maintain a serum albumin level of 3 g/dL.

Early in the course, albumin-treated patients had at least intermittently higher central venous pressure, higher mean arterial pressure, and less positive fluid balance. There was no difference in mortality at 28 days or 90 days, although the subset of patients with septic shock treated with albumin did have a lower mortality at 90 days (43.6% vs 49.9%; P = .03).

A growing body of literature suggests that hydroxyethyl starch solutions may cause renal damage, particularly in patients with sepsis.[2-5] Conversely, albumin has been suggested to confer benefit in sepsis resuscitation.[6,7]

In this study, albumin supplementation to maintain normal circulating serum albumin levels was not shown to be superior overall to crystalloid administration alone. This was true for starting the intervention earlier or later (< 6 hours vs 6-24 hours), and for outcomes measured earlier or later. But the subset of patients with septic shock did have statistically greater survival at 90 days, which raises the question of albumin superiority for this subgroup, and perhaps even as a later effect not related to the early resuscitation.[8]

Unfortunately, for general patient care, this study does not provide a definite answer. And the major question of whether different uses of albumin, such as in the earliest phases of fluid resuscitation and targeted to goals other than maintaining circulating level, still needs to be studied.

Esmolol May Stabilize Heart Rate in Septic Shock Patients.

For patients in septic shock who have an excessively high heartbeat, use of the beta blocker esmolol helped to lower and maintain heartbeat rates without adverse effects.

Andrea Morelli, MD, from the Department of Anesthesiology and Intensive Care, University of Rome, “La Sapienza,” Italy, and colleagues conducted a randomized phase 2 trial at the University of Rome hospital intensive care unit between November 2010 and July 2012. The researchers randomly assigned 154 patients whose heartbeats exceeded 95 beats per minute (BPM) and who required high doses of norepinephrine to receive either continuous infusion of esmolol to maintain heart rate between 80 and 94 BPM (n = 77) or to receive standard treatment (n = 77) of norepinephrine during intensive care unit stays.

The target heartbeat rate was achieved in all patients in the esmolol group and was significantly lower than for patients in the control group. The median heart rate reduction came to −28 BPM for the esmolol group compared with −6 BPM for the control group (P < .001). The median continuously infused dose for esmolol was 100 mg/h (interquartile range [IQR], 50 – 300 mg/h).

The mortality rate for the esmolol group came to 49.4% for the esmolol group compared with 80.5% for the control group (P < .001). Stroke volume index was significantly higher in the esmolol group (P = .02), as was the left ventricular stroke work index (P = .03). Fluid requirements were reduced in the esmolol group compared with controls (P < .001), although no clinically relevant differences existed between groups for some other cardiopulmonary variables.

“Compared with standard treatment, esmolol also increased stroke volume, maintained [mean arterial pressure], and reduced norepinephrine requirements without increasing the need of inotropic support or causing adverse effects on organ function,” the researchers write.

Because esmolol is short-acting and has a half-life of about 2 minutes, it enables rapid resolution of any potential adverse effects. These new findings, the researchers write, suggest esmolol “allows better ventricular filling during diastole, hence, improving stroke volume and thereby improving the efficiency of myocardial work and oxygen consumption.”

Limitations of the study include selection of a predefined arbitrary heart rate threshold and the requirement that the study be nonblinded and not placebo-controlled. In addition, results might not be similar in a less at-risk population.

Paves the Way

“This is the unblindable trial. There’s no way to blind this trial. That will always be a limitation of whatever comes down the road,” R. Phillip Dellinger, MD, professor and head of critical care medicine at Cooper University Hospital in Camden, New Jersey, told Medscape Medical News. Dr. Dellinger is first author of a recent articleon treatment guidelines for sepsis.

The new study, Dr. Dellinger said, “clears the way for a larger phase 3 trial, and it offers support for moving the physiology in the direction that would, on the surface, look beneficial. It shows that it’s safe. The secondary outcomes all moved in a positive direction or didn’t move at all. So there are no signals here of potential problems with doing this; instead there is evidence that it helps cardiac function.”

Some aspects of this phase 2 trial differ from many phase 2 trials, he added. “This trial picked a population that would be predicted to more likely benefit from beta blockage, which is requiring very high doses of norepinephrine and being tachycardic.” Limiting the trial population may be better than including a large population in a study and dividing them up in subgroup analyses, he said, but the results might not be generalizable to a larger population.

In summary, Dr. Dellinger said, “Even though the trial was small, I think it was encouraging.”

This research was funded by the Department of Anesthesiology and Intensive Care of the University of Rome, “La Sapienza.” Dr. Morelli reports receiving honoraria for speaking at Baxter symposia. One coauthor reports serving as a consultant for and receiving honoraria from speaking at Baxter. The other authors and Dr. Dellinger have disclosed no relevant financial relationships.

How polio changed my life.

Pulmão de Aço (Iron Lung), published this year in Brazil, tells the story of Eliana Zagui, a polio survivor who has lived for decades in a hospital in Brazil.

Pulmão de Aço (Iron Lung), published this year in Brazil, tells the story of Eliana Zagui, a polio survivor who has lived for decades in a hospital in Brazil.

By Eliana Zagui, author of Pulmão de Aço (Iron Lung)

Before it was eradicated through the effort of massive immunization campaigns in 1989, poliomyelitis was prevalent in Brazil. The lack of vaccine and poor sanitation in small towns resulted in thousands of victims a year. Avoiding polio was often a matter of luck.

In January 1976, at the age of two, my luck ran out. I woke up with a fever and weak lower limbs. Although my parents were used to my recurrent episodes of sore throat, they brought me to the nearest city of Jaboticabal for medical treatment. The next day, lacking a diagnosis, I was sent to Ribeirão Preto, a larger city with better medical facilities. By the time the doctors came to the conclusion that I had contracted polio, the virus had already started its devastating muscular paralysis process.

We lived in Guariba near São Paulo, more than 180 miles from the major polio treatment center in Brazil. Getting to the ‘Hospital das Clínicas’ in São Paulo was a struggle. But after several hours, we received a ride from a charitable individual. By that time, I was already paralyzed from my neck down, and my breathing was restricted by the paralysis of my diaphragm.

I was placed in an iron lung a number of times in an attempt to reverse the respiratory failure, but eventually the doctors concluded the battle was lost. I was tracheotomized and connected to an artificial respirator. More than 36 years later, I still depend on the artificial respirator to breathe.

I have lived the rest of my life at the same ‘Hospital das Clínicas.’ Out of  hundreds of children admitted to the hospital in the ‘60s and ‘70s, seven of us formed a family, and developed bonds with the doctors and nurses who looked after us. Five of our family died in the ‘80s, and now only Paulo Henrique Machado and I remain. We still share a room in the Intensive Care Unit.

It was in that room that Paulo and I learned how to read and write. While Paulo has limited hand movements, I can only move my neck and head. Everything I can do with some autonomy has to be done with my mouth. That includes my paintings, which are sold around the world through an association.

Dexmedetomidine Use in the ICU Are We There Yet?


Background Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an alpha-2 agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

MethodsObjective: The objective was to determine the efficacy of dexmedetomidine versus midazolam or propofol (preferred usual care) in maintaining sedation, reducing duration of mechanical ventilation, and improving patients’ interaction with nursing care.

Design: Two phase 3 multicenter, randomized, double-blind trials were conducted.

Setting: The MIDEX (Midazolam vs. Dexmedetomidine) trial compared midazolam with dexmedetomidine in ICUs of 44 centers in nine European countries. The PRODEX (Propofol vs. Dexmedetomidine) trial compared propofol with dexmedetomidine in 31 centers in six European countries and two centers in Russia.

Subjects: The subjects were adult ICU patients who were receiving mechanical ventilation and who needed light to moderate sedation for more than 24 hours.

Intervention: After enrollment, 251 and 249 subjects were randomly assigned midazolam and dexmedetomidine, respectively, in the MIDEX trial, and 247 and 251 subjects were randomly assigned propofol and dexmedetomidine, respectively, in the PRODEX trial. Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials were employed.

Outcomes: For each trial, investigators tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were the ability of the patient to communicate pain (measured by using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol (midazolam, n = 233, versus dexmedetomidine, n = 227; propofol, n = 214, versus dexmedetomidine, n = 223) population.

Results Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% confidence interval (CI) 0.97 to 1.18), and dexmedetomidine/propofol ratio in time at target sedation was 1.00 (95% CI 0.92 to 1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours, interquartile range (IQR) 67 to 337) versus midazolam (164 hours, IQR 92 to 380;P = 0.03) but not with dexmedetomidine (97 hours, IQR 45 to 257) versus propofol (118 hours, IQR 48 to 327; P= 0.24). Patient interaction (measured by using VAS) was improved with dexmedetomidine (estimated score difference versus midazolam 19.7, 95% CI 15.2 to 24.2; P <0.001; and versus propofol 11.2, 95% CI 6.4 to 15.9; P <0.001). Lengths of ICU and hospital stays and mortality rates were similar. Dexmedetomidine versus midazolam patients had more hypotension (51/247 [20.6%] versus 29/250 [11.6%]; P = 0.007) and bradycardia (35/247 [14.2%] versus 13/250 [5.2%]; P <0.001).

Conclusions Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved the ability of patients to communicate pain compared with midazolam and propofol. Greater numbers of adverse effects were associated with dexmedetomidine.



Sedation is commonly used in the intensive care unit (ICU) to reduce patient discomfort, improve tolerance with mechanical ventilation, prevent accidental device removal, and reduce metabolic demands during respiratory and hemodynamic instability.[1,2]Continuous and deep sedation have been associated with increased risk of delirium, longer duration of mechanical ventilation, increased length of ICU and hospital stays, and long-term risk of neurocognitive impairment, post-traumatic stress disorder, and mortality.[3–7] Sedation interruption and protocolized sedation have been associated with decreased length of ICU stay and reduced duration of mechanical ventilation.[4,5] Whether combining sedation interruption and protocolized sedation improves outcome is controversial. Whereas some studies show a benefit,[6] others show no difference.[8]

Commonly used first-line sedative medications, including propofol and midazolam, and less commonly used medications, such as lorazepam, have many side effects. There exists wide intra- and inter-individual variability,[9] resulting in unpredictable drug accumulation with benzodiazepines.[10] Lorazepam is associated with propylene glycol-related acidosis and nephrotoxicity. Propofol causes hypertriglyceridemia, pancreatitis, and propofol-related infusion syndrome.[11,12] Dexmedetomidine is a potent alpha-2 adrenoceptor agonist with an affinity for the alpha-2 adrenoceptor that is eight times higher than that of clonidine.[13] Prior data suggest that dexmedetomidine reduced duration of mechanical ventilation and resulted in earlier extubation.[14,15] In critically ill patients, use of dexmedetomidine has been associated with lower risk of delirium and coma compared with propofol, lorazepam, and midzolam.[15,16] However, safety and efficacy of prolonged dexmedetomidine infusion in the ICU have not been evaluated.

The PRODEX (Propofol vs. Dexmedetomidine) and MIDEX (Midazolam vs. Dexmedetomidine) trials attempted to answer this question with higher doses of dexmedetomidine for longer duration when compared with propofol and midazolam in mechanically ventilated patients. Both studies provide important clinical evidence that dexmedetomidine is an effective sedative agent compared with propofol and midazolam. Use of dexmedetomidine is associated with easier communication with patients, better assessment of pain (from the perspective of the caregiver), reduced delirium, and decreased time to extubation as compared with propofol. However, this finding did not translate into reduction of length of ICU or hospital stay. Among the strengths of the study are that it was a well-conducted, large, multicenter, double-blind, randomized controlled study. The trial employed frequent sedation assessment, daily sedation stops, and a double-dummy design to reduce the risk of bias.

Several important limitations to the study deserve further consideration. The weaning from mechanical ventilation and criteria for extubation were not standardized. Spontaneous breathing trials were performed in only about half of the sedation stops, as compared with approximately 60% of those screened in the Awakening and Breathing Controlled trial.[6] Whereas the incidence of neurocognitive disorders, including delirium, anxiety, and agitation, was evaluated throughout the study, the long-term neurocognitive and functional outcomes with dexmedetomidine have not been examined. Sedation was assessed from the caregivers’ perspective only, and future studies should include the patients’ perspective of quality of sedation. Also, this study included only patients with light to moderate sedation; thus, these findings may not be applicable to patients requiring deep sedation. In the first 24 hours of the PRODEX trial, discontinuation of dexmedetomidine was more frequent because of a lack of efficacy. As acknowledged by the authors of the PRODEX and MIDEX trials, most clinicians and centers do not consider dexmedetomidine an equivalent alternative to propofol and midazolam for long-term sedation. These trials, nevertheless, reassure clinicians regarding the safety of dexmedetomidine in terms of higher doses over a long period of time.

Recent guidelines of the Society of Critical Care Medicine recommend using non-benzodiazepine agents, such as propofol or dexmedetomidine, over benzodiazepines as a first-line sedative agent, and dexmedetomidine in patients at risk for delirium that is not related to alcohol and benzodiazepine use.[11] The opioid-sparing[11] effect of dexmedetomidine may reduce opioid requirements in critically ill patients. The most common side effects of dexmedetomidine are hypotension and bradycardia, and this limits its use in patients who are dependent on their cardiac output, such as patients in the acute phase of shock.



In carefully selected critically ill patients receiving prolonged mechanical ventilation, dexmedetomidine is safe and may be preferred as an alternative non-benzodiazepine agent to maintain light to moderate sedation. However, long-term outcomes, including neurocognitive effects, and the safety of dexmedetomidine are unknown.


Hydroxyethyl Starch Solutions Get Boxed Warning.

Hydroxyethyl starch solutions should not be used in critically ill patients, including those with sepsis and those admitted to the ICU, because they pose an increased risk for mortality and severe renal injury, the FDA has announced. A boxed warning will be added to the solutions’ labels to emphasize these risks.

Providers are also advised to avoid using HES solutions in patients with preexisting renal dysfunction. Treatment should be stopped at the first sign of renal injury; renal function should be monitored in all patients for 90 days after treatment.

In addition, the FDA says, HES solutions should be avoided in patients undergoing open heart surgery in association with cardiopulmonary bypass, given an increased risk for excessive bleeding. A separate warning about this risk will be added to the Warnings and Precautions section of the label.

Source: FDA


Effects of Patient-Directed Music Intervention on Anxiety and Sedative Exposure in Critically Ill Patients Receiving Mechanical Ventilatory SupportA Randomized Clinical Trial.


Importance  Alternatives to sedative medications, such as music, may alleviate the anxiety associated with ventilatory support.

Objective  To test whether listening to self-initiated patient-directed music (PDM) can reduce anxiety and sedative exposure during ventilatory support in critically ill patients.

Design, Setting, and Patients  Randomized clinical trial that enrolled 373 patients from 12 intensive care units (ICUs) at 5 hospitals in the MinneapolisSt Paul, Minnesota, area receiving acute mechanical ventilatory support for respiratory failure between September 2006 and March 2011. Of the patients included in the study, 86% were white, 52% were female, and the mean (SD) age was 59 (14) years. The patients had a mean (SD) Acute Physiology, Age and Chronic Health Evaluation III score of 63 (21.6) and a mean (SD) of 5.7 (6.4) study days.

Interventions  Self-initiated PDM (n = 126) with preferred selections tailored by a music therapist whenever desired while receiving ventilatory support, self-initiated use of noise-canceling headphones (NCH; n = 122), or usual care (n = 125).

Main Outcomes and Measures  Daily assessments of anxiety (on 100-mm visual analog scale) and 2 aggregate measures of sedative exposure (intensity and frequency).

Results  Patients in the PDM group listened to music for a mean (SD) of 79.8 (126) (median [range], 12 [0-796]) minutes/day. Patients in the NCH group wore the noise-abating headphones for a mean (SD) of 34.0 (89.6) (median [range], 0 [0-916]) minutes/day. The mixed-models analysis showed that at any time point, patients in the PDM group had an anxiety score that was 19.5 points lower (95% CI, −32.2 to −6.8) than patients in the usual care group (P = .003). By the fifth study day, anxiety was reduced by 36.5% in PDM patients. The treatment × time interaction showed that PDM significantly reduced both measures of sedative exposure. Compared with usual care, the PDM group had reduced sedation intensity by −0.18 (95% CI, −0.36 to −0.004) points/day (P = .05) and had reduced frequency by −0.21 (95% CI, −0.37 to −0.05) points/day (P = .01). The PDM group had reduced sedation frequency by −0.18 (95% CI, −0.36 to −0.004) points/day vs the NCH group (P = .04). By the fifth study day, the PDM patients received 2 fewer sedative doses (reduction of 38%) and had a reduction of 36% in sedation intensity.

Conclusions and Relevance  Among ICU patients receiving acute ventilatory support for respiratory failure, PDM resulted in greater reduction in anxiety compared with usual care, but not compared with NCH. Concurrently, PDM resulted in greater reduction in sedation frequency compared with usual care or NCH, and greater reduction in sedation intensity compared with usual care, but not compared with NCH.

Source: JAMA