Category Archives: Resus

Life-saving medicine

Acute Med, All Updates, ICU, Resus

Beta blockers potentially beneficial in septic shock

Leave a comment

Counterintuitive as it sounds, this is pretty cool. I blogged about these guys before when they published their findings on microcirculatory flow in septic patients given beta blockers.
It’s a small study – 77 patients with septic shock and a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of at least 65 mm Hg were randomised to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay. 77 patients received standard treatment. It should be noted the primary outcome (target heart rate) was not a patient-oriented endpoint. Interestingly though, there were no increased adverse events in the beta blocker group, which demonstrated improved left ventricular stroke work, lower lactate levels, decreased noradrenaline and fluid requirements, improved oxygenation, and a lower mortality.
Caution is appropriate here though: this study was a small, single-centre open-label trial. It will be very interesting to see if these effects are reproduced and whether they will ultimately translate to meaningful outcome benefits.
Read more about the study at the PulmCCM site.
There is also a great critical appraisal of the study at Emergency Medicine Literature of Note/a>.
Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial
JAMA. 2013 Oct 23;310(16):1683-91
[EXPAND Abstract]


IMPORTANCE: β-Blocker therapy may control heart rate and attenuate the deleterious effects of β-adrenergic receptor stimulation in septic shock. However, β-Blockers are not traditionally used for this condition and may worsen cardiovascular decompensation related through negative inotropic and hypotensive effects.

OBJECTIVE: To investigate the effect of the short-acting β-blocker esmolol in patients with severe septic shock.

DESIGN, SETTING, AND PATIENTS: Open-label, randomized phase 2 study, conducted in a university hospital intensive care unit (ICU) between November 2010 and July 2012, involving patients in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of 65 mm Hg or higher.

INTERVENTIONS: We randomly assigned 77 patients to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay and 77 patients to standard treatment.

MAIN OUTCOMES AND MEASURES: Our primary outcome was a reduction in heart rate below the predefined threshold of 95/min and to maintain heart rate between 80/min and 94/min by esmolol treatment over a 96-hour period. Secondary outcomes included hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization.

RESULTS: Targeted heart rates were achieved in all patients in the esmolol group compared with those in the control group. The median AUC for heart rate during the first 96 hours was -28/min (IQR, -37 to -21) for the esmolol group vs -6/min (95% CI, -14 to 0) for the control group with a mean reduction of 18/min (P <  .001). For stroke volume index, the median AUC for esmolol was 4 mL/m2 (IQR, -1 to 10) vs 1 mL/m2 for the control group (IQR, -3 to 5; P = .02), whereas the left ventricular stroke work index for esmolol was 3 mL/m2 (IQR, 0 to 8) vs 1 mL/m2 for the control group (IQR, -2 to 5; P = .03). For arterial lactatemia, median AUC for esmolol was -0.1 mmol/L (IQR, -0.6 to 0.2) vs 0.1 mmol/L for the control group (IQR, -0.3 for 0.6; P = .007); for norepinephrine, -0.11 μg/kg/min (IQR, -0.46 to 0.02) for the esmolol group vs -0.01 μg/kg/min (IQR, -0.2 to 0.44) for the control group (P = .003). Fluid requirements were reduced in the esmolol group: median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h(IQR, 4038 to 4775) for the control group (P < .001). We found no clinically relevant differences between groups in other cardiopulmonary variables nor in rescue therapy requirements. Twenty-eight day mortality was 49.4% in the esmolol group vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; P < .001).
CONCLUSIONS AND RELEVANCE: For patients in septic shock, open-label use of esmolol vs standard care was associated with reductions in heart rates to achieve target levels, without increased adverse events. The observed improvement in mortality and other secondary clinical outcomes warrants further investigation.

[/EXPAND]

Acute Med, All Updates, ICU, PHARM, Resus, Trauma

Colloids again: still no benefit.

Leave a comment

fluidinheloiconIt’s nice to have big randomised trials to guide critical care practice. The age-old crystalloid/colloid debate (is that still going?) has fueled a multicentre and multinational study in 2857 patients with hypovolaemic shock on intensive care units. Patients were classified as having sepsis, trauma, or other causes of hypovolaemic shock.
In the crystalloids group, allowed treatments included isotonic or hypertonic saline and any buffered solutions. In the colloids group, gelatins, albumin from 4-25%, dextrans, and hydroxyethyl starches were permitted.
The primary outcome of 28 day mortality was no different between groups. The study had an open-label design and recruitment took place over nine years.
This finding – no clinical benefit from colloids in critically ill patients – is in keeping with other major ICU trials of colloid therapy: Saline versus Albumin Fluid Evaluation (SAFE), Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP), Scandinavian Starch for Severe Sepsis/Septic Shock (6S), and the Crystalloid versus Hydroxyethyl Starch Trial (CHEST).
Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial
JAMA. 2013 Nov 6;310(17):1809-17
[EXPAND Abstract]

 

IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.

OBJECTIVE: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.

DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012.

INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.

MAIN OUTCOMES AND MEASURES: The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy.

RESULTS: Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03).

CONCLUSIONS AND RELEVANCE: Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy.

[/EXPAND]

Acute Med, All Updates, ICU, PHARM, Resus

Prehospital ECLS – it's happening

Leave a comment

Patients with refractory (>30 mins) cardiac arrest underwent prehospital cannulation for extracorporeal life support in a French feasibility study. A physician-paramedic team responded by car in Paris to cardiac arrest cases that met inclusion criteria. Mechanical CPR devices (Autopulse or LUCAS) were applied during cannulation. Femoral venoarterial ECMO was instituted using a Maquet Cardiohelp system. Blood products and inotropes, echocardiography, and hypothermia were included in the prehospital management package.
Seven patients were treated, with a mean age of 42 (+/- SD of 16, no median given). ECLS was started an average 57 min (±21) after the onset of ACLS. One patient survived to discharge neurologically intact. Two brain dead patients became organ donors. The survivor had hypertrophic cardiomyopathy with refractory ventricular fibrillation.
Safety and feasibility of prehospital extra corporeal life support implementation by non-surgeons for out-of-hospital refractory cardiac arrest
Resuscitation. 2013 Nov;84(11):1525-9
[EXPAND Abstract]


BACKGROUND: Extra corporeal life support (ECLS) has been recently introduced in the treatment of refractory cardiac arrest (CA). Several studies have assessed the use of ECLS in refractory CA once the patients reach hospital. The time between CA and the implementation of ECLS is a major prognostic factor for survival. The main predictive factor for survival is ECLS access time. Pre hospital ECLS implementation could reduce access time. We therefore decided to assess the feasibility and safety of prehospital ECLS implementation (PH-ECLS) in a pilot study.

METHODS AND RESULTS: From January 2011 to January 2012, PH-ECLS implementation for refractory CA was performed in 7 patients by a PH-ECLS team including emergency and/or intensivist physicians and paramedics. Patients were included prospectively and consecutively if the following criteria were met: they had a witnessed CA; CPR was initiated within the first 5min of CA and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. ECLS flow was established in all patients. ECLS was started 22min (±6) after the incision, and 57min (±21) after the onset of advanced cardiovascular life support (ACLS). In one patient, ECLS was stopped for 10min due to an accidental decannulation. One patient survived without sequelae. Three patients developed brain death.

CONCLUSIONS: This pilot study suggests that PH-ECLS performed by non-surgeons is safe and feasible. Further studies are needed to confirm the time saved by this strategy and its potential effect on survival.

[/EXPAND]

All Updates, ICU, PHARM, Resus

Hyperchloraemia and mortality

Leave a comment

Here’s something to add to the pile of data cautioning us to think before we acidify patients with saline. A study in Anesthesia and Analgesia using propensity matching provides retrospective evidence that patients who developed hyperchloremia after noncardiac surgery had worse outcomes.
For more information on why saline isn’t ‘normal’ see: What’s with all the chloride? An assault on salt
Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study
Anesth Analg. 2013 Aug;117(2):412-21
[EXPAND Abstract]


BACKGROUND: The use of normal saline is associated with hyperchloremic metabolic acidosis. In this study, we sought to determine the incidence of acute postoperative hyperchloremia (serum chloride >110 mEq/L) and whether this electrolyte disturbance is associated with an increase in length of hospital stay, morbidity, or 30-day postoperative mortality.

METHODS: Data were retrospectively collected on consecutive adult patients (>18 years of age) who underwent inpatient, noncardiac, nontransplant surgery between January 1, 2003 and December 31, 2008. The impact of postoperative hyperchloremia on patient morbidity and length of hospital stay was examined using propensity-matched and logistic multivariable analysis.

RESULTS: The dataset consisted of 22,851 surgical patients with normal preoperative serum chloride concentration and renal function. Acute postoperative hyperchloremia (serum chloride >110 mmol/L) is quite common, with an incidence of 22%. Patients were propensity-matched based on their likelihood to develop acute postoperative hyperchloremia. Of the 4955 patients with hyperchloremia after surgery, 4266 (85%) patients were matched to patients who had normal serum chloride levels after surgery. These 2 groups were well balanced with respect to all variables collected. The hyperchloremic group was at increased risk of mortality at 30 days postoperatively (3.0% vs 1.9%; odds ratio = 1.58; 95% confidence interval, 1.25-1.98) (relative risk 1.6 or risk increase of 1.1%) and had a longer hospital stay (7.0 days [interquartile range 4.1-12.3] compared with 6.3 [interquartile range 4.0-11.3]) than patients with normal postoperative serum chloride levels. Patients with postoperative hyperchloremia were more likely to have postoperative renal dysfunction. Using all preoperative variables and measured outcome variables in a logistic regression analysis, hyperchloremia remained an independent predictor of 30-day mortality with an odds ratio of 2.05 (95% confidence interval, 1.62-2.59).

CONCLUSION: This retrospective cohort trial demonstrates an association between hyperchloremia and poor postoperative outcome. Additional studies are required to demonstrate a causal relationship between these variables.

[/EXPAND]

Acute Med, All Updates, Guidelines, ICU, PHARM, Resus

Guidelines for the Management of Heart Failure

Leave a comment

Some new guidelines to be aware of are the AHA Guidelines for the Management of Heart Failure. Full text is available free and while comprehensively covering chronic heart failure there is an interesting section on acute decompensated heart failure.
Evidence-based medicine enthusiasts might be interested in recommendations to consider dopamine, nesiritide, and ultrafiltration. These therapies also get a mention in the 2012 European Guidelines. I recommend you review the articles cited in the guidelines to make your own mind up.
Here are a couple of snippets you may find useful:


Snippet from American Guidelines: intravenous loop diuretic doses

“HF patients receiving loop diuretic therapy should receive an initial parenteral dose greater than or equal to their chronic oral daily dose; then dose should be serially adjusted.”


Snippet from European Guidelines: management algorithm for acute heart failure

Click to enlarge

AHF-ESC

2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary
Circulation. 2013 Oct 15;128(16):1810-52 Free Full Text
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012
Eur Heart J. 2012 Jul;33(14):1787-847 Free Full Text

All Updates, ICU, Resus

Avoiding intubation in ARDS with awake ECMO

Leave a comment

ECMOillusiconA letter in Intensive Care Medicine by Hoeper and colleagues from Hannover describes a small case series of six ARDS patients with severe hypoxaemia who went straight from non-invasive ventilation to awake veno-venous ECMO. All had single organ failure and four were immunocompromised, the latter factor influencing the decision to try to avoid invasive mechanical ventilation. Four of the six patients survived to hospital discharge. A larger multicentre study is being planned.

Clinical illustration courtesy of Dr Brian Burns

Extracorporeal membrane oxygenation instead of invasive mechanical ventilation in patients with acute respiratory distress syndrome
Intensive Care Med. 2013 Nov;39(11):2056-2057 (no abstract)

All Updates, Fascinomata, Resus

Even the dead exhale CO2

Leave a comment

cadaverETCO2iconCardiac arrest patients sometimes have unrecognised oesophageal intubations because clinicians omit capnography, based on the assumption that circulatory arrest leads to an absence of exhaled CO2. This is wrong, and reassuringly the latest ILCOR cardiac arrest guidelines recommend waveform capnography during resuscitation.
Of interest is the fact that even corpses have CO2 in their lungs. While not clinically relevant, this may have value when fresh frozen cadavers are used for airway training, since we might be able to supplement the realism of airway instrumentation with the realism of connecting the capnography adaptor and circuit and seeing confirmation on the monitor.
This preliminary study, completed by my Sydney HEMS colleagues, needs further work, but it’s an interesting area.
Sustained life-like waveform capnography after human cadaveric tracheal intubation
Emerg Med J doi:10.1136/emermed-2013-203105
[EXPAND Abstract]


Introduction Fresh frozen cadavers are effective training models for airway management. We hypothesised that residual carbon dioxide (CO2) in cadaveric lung would be detectable using standard clinical monitoring systems, facilitating detection of tracheal tube placement and further enhancing the fidelity of clinical simulation using a cadaveric model.

Methods The tracheas of two fresh frozen unembalmed cadavers were intubated via direct laryngoscopy. Each tracheal tube was connected to a self-inflating bag and a sidestream CO2 detector. The capnograph display was observed and recorded in high-definition video. The cadavers were hand-ventilated with room air until the capnometer reached zero or the waveform approached baseline.

Results A clear capnographic waveform was produced in both cadavers on the first postintubation expiration, simulating the appearances found in the clinical setting. In cadaver one, a consistent capnographic waveform was produced lasting over 100 s. Maximal end-tidal CO2 was 8.5 kPa (65 mm Hg). In cadaver two, a consistent capnographic waveform was produced lasting over 50 s. Maximal end-tidal CO2 was 5.9 kPa (45 mm Hg).

Conclusions We believe this to be the first work to describe and quantify detectable end-tidal capnography in human cadavers. We have demonstrated that tracheal intubation of fresh frozen cadavers can be confirmed by life-like waveform capnography. This requires further validation in a larger sample size.

[/EXPAND]

All Updates, ICU, PHARM, Podcasts, Resus

How to Be a Hero

Leave a comment

Kal-fly-iconI’m not a hero and don’t claim to be, but when I was given this talk to do for the SMACC 2013 conference I researched the topic and realised I’d worked with several of them.
The talk was the toughest I’ve ever given, because I cried while giving it, and knew that it wouldn’t just be the large audience in front of me who would know I was a wuss, but that it was being recorded for many others to find out too!

A full transcript of the talk, the slide set, and links to references from the talk can be found here.

Acute Med, All Updates, ICU, Resus

Early surgery for intracerebral haemorrhage

Leave a comment

ICHgraphicIconTo operate or not to operate on patients with an intracerebral haematoma? Deep ones can be tricky and risk damage to surrounding brain, so superficial ones may be more likely to benefit.
These patients with superficial lesions were assessed in STICH II, an international prospective randomised controlled trial comparing early surgery with conservative treatment.
Inclusion criteria were strict:

  • spontaneous lobar intracerebral haemorrhage on CT scan (≤1 cm from the cortical surface of the brain) with a volume of between 10 mL and 100 mL
  • within 48 h of onset
  • had a best motor score on the Glasgow Coma Score (GCS) of 5 or 6, and had a best eye score of 2 or more (ie, were conscious at randomisation).

The primary outcome was a Glasgow Outcome Scale-based evaluation of recovery (‘favourable’ vs ‘unfavourable’), which did not significantly differ between groups.
A predefined subgroup of patients with a poorer prognosis (using a score based on age, haematoma size and GCS) may have a better outcome with surgery. Some patients randomised to conservative therapy subsequently underwent delayed surgery. Thanks to appropriate intention-to-treat analysis they would have remained in the conservative treatment group which may have contributed to an underestimation of the benefit of surgery.
So, overall a negative trial, and patients with small lesions and higher GCS scores won’t benefit from surgery. Patients in poorer prognostic groups might benefit, but that remains unproven.
Some other ICH trials to be aware of are Clear III and MISTIE III, which are investigating thrombolytic agents in combination with clot removal, including with minimally invasive techniques.
Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial
Lancet. 2013 Aug 3;382(9890):397-408
[EXPAND Abstract]


BACKGROUND: The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10-100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients.

METHODS: In this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967.

FINDINGS: 307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI -4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367).

INTERPRETATION: The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage.

[/EXPAND]

Acute Med, All Updates, ICU, Resus

Beta blockade in sepsis

Leave a comment

tachy-iconWhat do septic patients need if they remain shocked after fluid resuscitation? Catecholamines right? Let’s stimulate some adrenoceptors and support that circulation!
Sydney’s Prof Myburgh has told us why adrenaline (epinephrine) and noradrenaline (norepinephrine) are the go-to vasoactive choices, and Prof Singer from London likes to remind us about the detrimental effects of these drugs – the pros and cons are listed here. Tachycardia is associated with worse outcomes in sepsis, and the balance of oxygen supply and demand can be difficult to achieve. Beta blocking drugs could reduce tachycardia, but there does seem to be something counter-intuitive about giving both beta-blockers and catecholamines in the same patient. You might expect that beta blockers would cause fall in cardiac output and worsen tissue perfusion.
A small study previously showed possible helpful effects of beta blockers in children with burns. The potential benefits may extend beyond control of heart rate to anti-inflammatory / anti-catabolic effects. A recent publication evaluated beta blockers in adult patients with septic shock, which appears to be a pilot study for an ongoing randomised controlled trial.
They included patients who had been fluid resuscitated and who required noradrenaline, and treated them with a titrated esmolol infusion commenced at 25 mg/hr, with an upper dose limit of 2,000 mg/hr, to maintain a predefined HR range between 80 and 94 beats per minute. Esmolol was chosen because of its half-life of approximately 2 min, so any adverse effects could be rapidly reversed. They examined the macrocirculation using pulmonary artery catheterisation and the microcirculation using sublingual microvascular blood flow imaging.
Most of the patients had pneumonia, and interestingly, all patients received intravenous hydrocortisone (200mg/d) as a continuous infusion.
In this small cohort of patients, they found that titrating the heart rate to less than 95 bpm was associated with maintenance of stroke volume and preservation of microvascular blood flow. Although cardiac output fell because of the lower HR, stroke volume, MAP, and lactate levels were unchanged while noradrenaline requirements were reduced.

Increased vascular reactivity to norepinephrine following nonselective β-blockade is supported by volunteer and animal studies, and postulated mechanisms include:

  • blockade of a peripheral β2-mediated vasodilatory effect of noradrenaline
  • decreased clearance of infused noradrenaline
  • a centrally mediated effect on reflex activity
  • inhibition of vascular endothelial nitric oxide synthase activity

Microvascular Effects of Heart Rate Control With Esmolol in Patients With Septic Shock: A Pilot Study
Crit Care Med. 2013 Sep;41(9):2162-2168
[EXPAND Abstract]

 

OBJECTIVE: β-blocker therapy may control heart rate and attenuate the deleterious effects of β-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the β-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation.

DESIGN: Prospective, observational clinical study.

SETTING: Multidisciplinary ICU at a university hospital.

MEASUREMENTS AND MAIN RESULTS: After 24 hours of initial hemodynamic optimization, 25 septic shock patients with a heart rate greater than or equal to 95 beats per minute and requiring norepinephrine to maintain mean arterial pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory blood flow was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 24 hours after esmolol administration. Heart rates targeted between 80 and 94 beats per minute were achieved in all patients. Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m; p < 0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m; p = 0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p = 0.002), while the heterogeneity index decreased (median 0.06 [interquartile range 0; 0.21] vs 0 [0; 0]; p = 0.002). PaO2 and pH increased while PaCO2 decreased (all p < 0.05). Of note, norepinephrine requirements were significantly reduced by selective β-1 blocker therapy (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] µg/kg/min; p = 0.03).

CONCLUSIONS: This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements.

[/EXPAND]