Speedy sepsis care, intubation after cardiac arrest, and more

Summaries from ACP Hospitalist Weekly.

Severe sepsis patients getting earlier antibiotics were less likely to develop shock

Earlier initiation of antibiotics was associated with lower risk of developing septic shock among ED patients with severe sepsis, a recent study found.

The retrospective cohort study included 3,929 adult patients diagnosed in an urban academic medical center with severe sepsis. All studied patients received antibiotics within 24 hours, and patients were excluded if they presented with shock. The overall mortality rate was 12.8%. Results were published online by Critical Care Medicine on Feb. 6 and appeared in the April issue.

Twenty-five percent of the patients progressed to sepsis shock. Patients who progressed to shock had a significantly longer median time to antimicrobial administration than those who did not (3.77 hours vs. 2.76 hours; P<0.001). Each hour until antimicrobial administration was associated with an 8% increase in progression. Time to administration was also associated with in-hospital mortality (odds ratio, 1.05; 95% CI, 1.03 to 1.07).

After multivariate logistic regression, study authors identified several factors associated with progression to shock: in addition to time to antimicrobials, also male sex, Charlson Comorbidity Index, and number of infections. Factors associated with shorter time to antimicrobial administration included age, white blood cell count, hypotension, and respiratory/lung infection.

The results indicate that not only do antibiotics inhibit progression to septic shock, “it seems that they do so in the sickest patients of the cohort, principally because they are administered earlier in these patients,” the authors said. The study emphasizes the importance of administering broad-spectrum antibiotics to severe sepsis patients as early as possible and identifies other risk factors for progression that may allow better prognostication for severe sepsis patients, the authors concluded.

The study was limited by its use of ICD-9 codes to identify patients with severe sepsis and septic shock, which likely resulted in some patients with these conditions being missed. Patients with systemic inflammatory response syndrome but no organ dysfunction would also have been excluded, but this would make the study's criteria fairly similar to the new Sepsis-3 definitions, the authors said.

Intubation after in-hospital cardiac arrest not associated with benefit, study finds

Patients who were intubated within 15 minutes of in-hospital cardiac arrest had worse survival and functional outcomes than patients who were not intubated, a study found.

The observational cohort study used the Get With The Guidelines-Resuscitation registry to identify 108,079 patients who underwent in-hospital cardiac arrest between January 2000 and December 2014. Overall, 22.4% of them survived to hospital discharge, the study's primary outcome. Results were published online by JAMA on Jan. 24 and appeared in the Feb. 24 issue.

Intubation occurred within 15 minutes of arrest in 71,615 patients. Of these, 60.5% (43,314 patients) were matched to patients who were not intubated in the same minute after arrest. Compared to the non-intubated patients, the intubated patients were less likely to survive to discharge (16.3% vs. 19.4%; risk ratio, 0.84; 95% CI, 0.81 to 0.87; P<0.001). They were also significantly less likely to have return of spontaneous circulation (57.8% vs. 59.3%) or to have a good functional outcome, defined as a cerebral performance category score of 1 or 2 (10.6% vs. 13.6%).

“Although the study design does not eliminate the potential for confounding by indication, these findings do not support early tracheal intubation for adult in-hospital cardiac arrest,” the study authors concluded. They noted that although intubation was not associated with improved outcomes in any studied subgroup, there were some differences by subgroup, including that patients with an initial shockable rhythm had a particularly large decrease in survival if they were intubated and that patients with preexisting respiratory insufficiency had no difference in outcomes associated with intubation.

If the association between intubation and poor outcomes is found to be causal, multiple mechanisms could explain it, including interruption in chest compressions, delays in defibrillation or epinephrine administration, hyperventilation and hyperoxia, inadequate oxygenation during intubation attempts, or unrecognized esophageal intubation or dislodgement of the tube, the study authors wrote. They said that randomized controlled trials of intubation in such patients are justified but would need to be very large to show an effect.

Because of the risk of confounding, the study leaves uncertainty about whether intubation in these situations is or is not harmful, according to an accompanying editorial. “This is hardly a ringing endorsement for such an established intervention that requires substantial cost to provide, considering both the training and staffing costs and the downstream costs of mechanical ventilation and intensive care that are incurred once the patient is intubated,” the editorialist wrote.

Repeated Holter monitoring after stroke identified afib

In patients who recently had an acute ischemic stroke, prolonged Holter monitoring identified significantly more cases of atrial fibrillation than standard care, a recent study found.

The open-label trial included patients in Germany who were 60 years or older when they presented with an acute ischemic stroke and sinus rhythm and no history of atrial fibrillation. The patients were randomized to 10 days of Holter EKG monitoring at baseline, 3 months, and 6 months (n=200) or standard care, including at least 24 hours of rhythm monitoring (n=198). Results were published online by The Lancet Neurology on Feb. 7 and appeared in the April issue.

Photo by Thinkstock
Photo by Thinkstock

After six months of follow-up, atrial fibrillation or flutter of at least 30 seconds had been detected in 14% of the monitoring group and 5% of the control group (difference, 9%; 95% CI, 3.4% to 14.5%; P=0.002). Researchers calculated a number needed to screen of 11. They concluded that the enhanced monitoring was better than standard care and should be considered in such patients if detection of atrial fibrillation would change medical management (e.g., initiation of anticoagulation).

Most atrial fibrillation cases (67%) were identified in the first 10-day monitoring period, the authors noted. This finding led them to propose a stepwise approach—all patients in whom the detection of atrial fibrillation would be of therapeutic relevance could receive seven to 10 days of monitoring beginning within the first days after stroke, and if results were negative, the decision to conduct additional monitoring would be based on patients' individual risk for atrial fibrillation. The authors noted that although the study was not powered for clinical endpoints, the monitored group had a lower rate of recurrent stroke and transient ischemic attack than the control group. The study was funded by a pharmaceutical company.

Although the study's results support potential benefits from monitoring, several questions about the relationship between atrial fibrillation and stroke remain unanswered, said an accompanying comment. It's not established whether cardiac arrhythmias detected after cerebral injury are the cause or consequence of strokes, and given the prevalence of atrial fibrillation in the general population, the prognostic significance of isolated and short-lasting atrial arrhythmias needs further investigation, according to the editorialist.

High-flow nasal cannulas may be more reliable than noninvasive ventilation in some cases

For patients with acute respiratory failure, high-flow nasal cannulas may reduce the rate of endotracheal intubation compared to conventional oxygen therapy, a study found.

Researchers reviewed the literature for studies that compared high-flow nasal cannulas (HFNCs) with noninvasive positive-pressure ventilation (NIPPV) and conventional oxygen therapy in adult patients with acute respiratory failure. The primary outcome was the rate of endotracheal intubation. Secondary outcomes included ICU mortality and ICU length of stay. Results were published online Jan. 19 by CHEST and appeared in the April issue.

The analysis included 18 trials comprising 3,881 patients. Compared with conventional oxygen therapy, HFNC was associated with a lower rate of endotracheal intubation (odds ratio [OR], 0.47; 95% CI, 0.27 to 0.84; P=0.01). The difference was also significant compared to both other groups combined (OR, 0.60; 95%, CI, 0.41 to 0.86; P=0.006), but there was no significant difference in comparison with NIPPV (OR, 0.73; 95% CI, 0.47 to 1.13; P=0.16).

Also, ICU mortality was not significantly different in patients receiving HFNC and those on conventional oxygen therapy (OR, 0.65; 95% CI, 0.37 to 1.13; P=0.13) or NIPPV (OR, 0.63; 95% CI 0.34 to 1.18; P=0.15) or both groups combined (OR, 0.67; 95% CI, 0.44 to 1.01; P=0.05).

Researchers noted that HFNC decreased the need for endotracheal intubation in adult patients with acute respiratory failure, similar to NIPPV and better than conventional oxygen. However, HFNC was not associated with any improvement in ICU mortality or decrease in ICU length of stay compared with NIPPV or conventional oxygen.

Numerous factors besides respiratory status may contribute to ICU mortality and ICU length of stay, especially complications such as acute kidney dysfunction and cardiac impairment, the researchers said. “Moreover, it is undeniable that medical resources as well as expenditures are tightly related to the disease outcomes, such as bed availability in general wards and insurance status, which to some extent may offset the positive effects of HFNC,” they wrote.

The authors concluded, “With similar respiratory mechanics and equivalent clinical outcomes but better compliance and fewer complications, HFNC may serve as a reliable substitute of NIPPV, especially in patients after extubation.”

No added benefit of more than 3 days of antibiotics in patients with suspected VAP and minimal ventilator settings, study finds

A very short course of antibiotics produced similar mortality outcomes to a longer course in patients treated for suspected ventilator-associated pneumonia (VAP) who had minimal, stable ventilator settings, a recent study found.

At a single hospital, researchers retrospectively identified adult patients started on antibiotics for possible VAP who had minimal and stable ventilator settings for at least three days (daily minimum positive end-expiratory pressure [PEEP] of ≤5 cm H2O and daily minimum fraction of inspired oxygen [FiO2] of ≤40% on the day antibiotics were started and the following two calendar days). Results were published online on Dec. 29, 2016, by Clinical Infectious Diseases.

Of 1,290 patients, 259 were prescribed one to three days of antibiotics, and 1,031 were prescribed more than three days of antibiotics. Researchers compared the following outcomes between the two groups: time to extubation alive, ventilator death, time to hospital discharge alive, and hospital death.

In general, patients in both groups were similar in sex, race, unit type, comorbidities, and initial clinical characteristics. Patients in the short-course group were prescribed a median of two days of antibiotics, compared to a median of nine days in the long-course group.

In unadjusted analyses, researchers found no significant differences between the groups in mean duration of mechanical ventilation, hospital length of stay, or hospital mortality rates. The median numbers of days from antibiotic start to extubation and hospital discharge were longer in the long-course group.

After adjusting for confounders (e.g., comorbidities, severity of illness, temperature, white blood cell count, vasopressor requirement, pulmonary specimen characteristics, and culture results), researchers found no significant differences between groups in the hazard ratios (HRs) for time to extubation alive (HR, 1.16 for short-course treatment; P=0.08), ventilator death (HR, 0.82; P=0.32), time to hospital discharge alive (HR, 1.07; P=0.43), or hospital death (HR, 0.99; P=0.96). The point estimates for these outcomes consistently favored short-course patients. Results of three propensity-matched analyses eliminated observable differences between the two groups.

Limitations of the study include its retrospective, observational, single-center design and the possibility of unmeasured confounders, the study authors wrote. In particular, they noted that clinicians may have selected shorter courses because the patients were less ill or had less severe pneumonia, or because they were less confident in the diagnosis. They added that these findings should be further evaluated in a randomized controlled trial.

If confirmed, these results may offer clinicians a simple, objective, and inexpensive way to identify potential candidates for early discontinuation of antibiotics, they noted. “Clinicians will simply need to track patients' ventilator settings: those with daily minimum PEEPs of ≤5 cm H2o and daily minimum Fio2s<40% for at least 3 days from the first day of antibiotics may be suitable candidates for early antibiotic discontinuation,” they wrote.

Patients on NOACs, warfarin, or neither responded similarly to rt-PA treatment

Patients taking a non-vitamin K antagonist oral anticoagulant (NOAC) who had an ischemic stroke appeared to have similar outcomes from recombinant tissue plasminogen activator (rt-PA) treatment as those taking warfarin or no anticoagulant, a recent study found.

The observational retrospective study used data from the Get With The Guidelines-Stroke registry to compare outcomes among 42,887 patients who received rt-PA within 4.5 hours of an ischemic stroke. Two hundred fifty-one of the patients were taking a NOAC (87 on dabigatran, 129 on rivaroxaban, and 35 on apixaban), 1,500 were taking warfarin, and 41,136 were taking neither. Results were published in Circulation on Jan. 24 and appeared in the March 14 issue.

Unadjusted rates of symptomatic intracranial hemorrhage were 4.8% in NOAC patients, 4.9% in warfarin patients, and 3.9% in no-anticoagulation patients. However, patients on NOACs or warfarin were older, had more comorbid conditions, and had more severe strokes than the other patients. After adjustment for those factors, the study found no difference in intracranial hemorrhage rates among the groups. There were also no significant differences in life-threatening or serious systemic hemorrhage, any rt-PA complication, inpatient mortality, or modified Rankin Scale score at discharge.

“Collectively, these preliminary experiences suggest that giving intravenous rt-PA to selected patients who were receiving NOACs before stroke is not associated with markedly elevated risks and must be weighed against the risk of prolonged morbidity from stroke if rt-PA is withheld,” the authors wrote. Although the authors believe their study is the largest to date on this issue, it was limited by its size, as well as lack of data on the timing of the last NOAC dose, coagulation markers, and use of reversal agents (although none were commercially available at the time).

Current American Heart Association/American Stroke Association guidelines, based on expert opinion, contraindicate rt-PA in patients on NOACs unless the last intake was at least 48 hours earlier or relevant laboratory tests are normal, the authors noted. The current study's findings should be considered preliminary, according to the authors, who are now conducting another similar study with data on last intake of NOACs, coagulation test results, and postdischarge outcomes.

Fever treatment does not improve 28-day mortality in critically ill adults with sepsis, review finds

Antipyretic treatment does not significantly improve 28-day or hospital mortality in critically ill adult patients with sepsis, a recent systematic review and meta-analysis found.

The primary outcomes were 28-day and hospital mortality, and secondary outcomes included early mortality (i.e., death in the ICU or prior to day 14 after enrollment), frequency of acquisition of nosocomial infections, frequency of shock reversal, and mean changes in body temperature, heart rate, and minute ventilation with antipyretic treatment.

Photo by Thinkstock
Photo by Thinkstock

Researchers separately analyzed eight randomized studies of 1,507 patients and eight observational studies of 17,432 patients. Results were published online on Feb. 17 and in the May issue of Critical Care Medicine.

Of the randomized trials, four reported 28-day mortality and four reported hospital mortality. Comparing antipyretic therapy to control, pooled relative risk (RR) for the primary mortality outcomes was 0.93 (P=0.36). Antipyretic therapy was associated with significant decreases in early mortality (RR, 0.68; P=0.01) and postintervention temperature (mean difference, −0.38 °C; P<0.003) but had no significant effects on other secondary outcomes. Of the observational studies, six studies of 2,058 patients were included in the analysis of 28-day/hospital mortality, and two studies of 15,374 patients were included in the analysis of early mortality. The pooled odds ratio was 0.90 (P=0.70) for 28-day or hospital mortality.

Although randomized studies showed significantly lower early mortality with antipyretic treatment, the study authors noted that the importance of improved early mortality “is questionable as a patient-centered outcome, and this finding should not influence clinical practice.” One hypothesis for the decrease in early (and not later) mortality is that controlling fever blunts the immunologic benefit of hyperthermia, leading to increased nosocomial infections later in the hospital course, they added.

Limitations of the analysis include the enrollment of both febrile and afebrile patients across studies and variations in the interventions being evaluated (e.g., nonsteroidal anti-inflammatory drugs, acetaminophen, physical cooling) and the duration of treatment.