Tag Archives: drugs

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

Drugs in cardiac arrest – guess what works?

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Just like epinephrine (adrenaline), amiodarone does not increase survival to hospital discharge in cardiac arrest patients. I doubt his will deter the people in the resuscitation room with their stopwatches from handing me these drugs and telling me I ought to be giving them though.

Amiodarone - a load of balls

 

AIMS: In adult cardiac arrest, antiarrhythmic drugs are frequently utilized in acute management and legions of medical providers have memorized the dosage and timing of administration. However, data supporting their use is limited and is the focus of this comprehensive review.

METHODS: Databases including PubMed, Cochrane Library (including Cochrane database for systematic reviews and Cochrane Central Register of Controlled Trials), Embase, and AHA EndNote Master Library were systematically searched. Further references were gathered from cross-references from articles and reviews as well as forward search using SCOPUS and Google scholar. The inclusion criteria for this review included human studies of adult cardiac arrest and anti-arrhythmic agents, peer-review. Excluded were review articles, case series and case reports.

RESULTS: Of 185 articles found, only 25 studies met the inclusion criteria for further review. Of these, 9 were randomised controlled trials. Nearly all trials solely evaluated Ventricular Tachycardia (VT) and Ventricular Fibrillation (VF), and excluded Pulseless Electrical Activity (PEA) and asystole. In VT/VF patients, amiodarone improved survival to hospital admission, but not to hospital discharge when compared to lidocaine in two randomized controlled trials.

CONCLUSION: Amiodarone may be considered for those who have refractory VT/VF, defined as VT/VF not terminated by defibrillation, or VT/VF recurrence in out of hospital cardiac arrest or in-hospital cardiac arrest. There is inadequate evidence to support or refute the use of lidocaine and other antiarrythmic agents in the same settings.

The use of antiarrhythmic drugs for adult cardiac arrest: A systematic review
Resuscitation. 2011 Jun;82(6):665-70

Acute Med, All Updates, ICU, Resus

LRAs for acute asthma?

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As far as I’m concerned the jury is still out here since this small study was terminated early, more patients in the montelukast group received magnesium and / or aminophylline, and it is unclear how the groups compared with regard to other other acute therapies such as beta-agonists and steroids.

BACKGROUND: Although leukotriene receptor antagonists have an established role in the management of patients with chronic asthma, their efficacy in an acute asthma exacerbation is not fully known.
METHODS: 87 adults with acute asthma requiring hospitalisation were randomly assigned to receive either montelukast 10 mg or placebo on admission and every evening thereafter for 4 weeks (when they were reviewed as outpatients). All patients were admitted under the care of a consultant chest physician and received full care for acute asthma according to the British Thoracic Society guidelines. The primary end point was the difference in peak expiratory flow (PEF) between active and placebo treatment the morning following admission.
RESULTS: Primary end point data were analysed for 73 patients. At study entry, patients who received montelukast (n=37) had a mean (±SD) PEF of 227.6 (±56.9) l/min (47.6% predicted) and those who received placebo (n=36) had a PEF of 240.3 (±99.8) l/min (49.6% predicted). The morning after admission, patients who received montelukast achieved a PEF of 389.6 (±109.7) l/min (81.4% predicted) compared with 332.3 (±124.9) l/min (69.8% predicted) for placebo (p=0.046). The mean difference between treatment groups was 57.4 l/min (95% CI of 1.15 to 113.6 l/min or 1.95-21.2% predicted).
CONCLUSION: In acute asthma exacerbations the additional administration of oral montelukast results in a significantly higher PEF the morning after admission than that achievable with current standard treatment.

Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial
Thorax. 2011 Jan;66(1):7-11

Acute Med, All Updates, ICU, Resus

Vasoactive drugs in cardiogenic shock

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I’m always on the look-out for evidence to guide vasoactive drug therapy, an area where much dogma is spouted by many who have not read the literature. Here’s a small (note: pilot) study comparing two strategies for cardiogenic shock. The higher heart rate and lactate with epinephrine (adrenaline) are consistent with the findings of the great CAT study; this is of interest, but not necessarily clinically significant nor practice changing.

OBJECTIVE: There is no study that has compared, in a randomized manner, which vasopressor is most suitable in optimizing both systemic and regional hemodynamics in cardiogenic shock patients. Hence, the present study was designed to compare epinephrine and norepinephrine-dobutamine in dopamine-resistant cardiogenic shock.
DESIGN: Open, randomized interventional human study.
SETTING: Medical intensive care unit in a university hospital.
PATIENTS: Thirty patients with a cardiac index of <2.2 L/min/m and a mean arterial pressure of <60 mm Hg resistant to combined dopamine-dobutamine treatment and signs of shock. Patients were not included in cases of cardiogenic shock secondary to acute ischemic events such as myocardial infarction. Noninclusion criteria also included immediate indication of mechanical assistance.
INTERVENTIONS: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain a mean arterial pressure of between 65 and 70 mm Hg with a stable or increased cardiac index.
MAIN RESULTS: Both regimens increased cardiac index and oxygen-derived parameters in a similar manner. Patients in the norepinephrine-dobutamine group demonstrated heart rates lower (p<.05) than those in the epinephrine group. Epinephrine infusion was associated with new arrhythmias in three patients. When compared to baseline values, after 6 hrs, epinephrine infusion was associated with an increase in lactate level (p<.01), whereas this level decreased in the norepinephrine-dobutamine group. Tonometered PCO2 gap, a surrogate for splanchnic perfusion adequacy, increased in the epinephrine-treated group (p<.01) while decreasing in the norepinephrine group (p<.01). Diuresis increased in both groups but significantly more so in the norepinephrine-dobutamine group, whereas plasma creatinine decreased in both groups.
CONCLUSIONS: When considering global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, epinephrine is associated with a transient lactic acidosis, higher heart rate and arrhythmia, and inadequate gastric mucosa perfusion. Thus, the combination norepinephrine-dobutamine appears to be a more reliable and safer strategy.

Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study
Crit Care Med. 2011 Mar;39(3):450-5

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

Cardiac arrest drugs and pupils

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Although not predictive immediately post-cardiac arrest in the emergency department, dilated unreactive pupils two or three days later on the ICU may indicate a hopeless prognosis. We know from our experience with adrenaline (epinephrine) infusions that this drug does not prevent pupils from reacting to light, but what about atropine?

A letter by Dr Sophie MacDougall-Davis in Resuscitation describes a 66 year old male patient admitted to the ICU after an intraoperative PEA arrest during which he received 3 mg intravenous atropine. Post arrest and post anaesthesia he was awake with no neurological deficit, but eight hours after the cardiac arrest his pupils remained fixed and dilated, and were dilated with only a very slight reaction the next morning and remained sluggish at forty-eight hours, normalising at seventy-two hours. A possible reason for its prolonged action may be uptake of atropine from the plasma into the aqueous humor of the eye, followed by its slow release.
Dr MacDougall-Davis cautions:

When assessing pupils in comatose cardiac arrest survivors, the potential for atropine to have a prolonged effect on pupil size and reactivity should be considered.

Atropine, fixed dilated pupils and prognostication following cardiac arrest
Resuscitation. 2011 Feb;82(2):232

All Updates, ICU, Resus

Longer apnoea time with roc in the obese too

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Suxamethonium increases muscle oxygen consumption as a result of skeletal muscle fasciculation. In a comparison between sux and rocuronium in rapid sequence intubation, this resulted in faster desaturation in the sux group. A further study demonstrates a similar finding in obese patients.

BACKGROUND: Rapid sequence induction may be associated with hypoxemia. The purpose of this study was to investigate the possible difference in desaturation during rapid sequence induction in overweight patients using either succinylcholine or rocuronium.
METHODS: Sixty patients with a body mass index (BMI) between 25 and 30 kg/m², American Society of Anesthesiologists class I or II, undergoing general anesthesia were randomly divided into a succinylcholine group and a rocuronium group. After a 3-min preoxygenation, patients received rapid sequence induction of general anesthesia with midazolum-fentanyl-propofol and succinylcholine (1.5 mg/kg) or rocuronium (0.9 mg/kg). Ventilation was not initiated until oxygen saturation declined to 92%. We measured the times when oxygen saturation reached 98%, 96%, 94% and 92%. Safe Apnea Time was defined as the time from administration of neuromuscular blocking drugs to oxygen saturation fell to 92%. The recovery period was defined as the time from initiation of ventilation until oxygen saturation was 97%. Arterial blood gases were taken at baseline, after preoxygenation and at 92% oxygen saturation.
RESULTS: The mean Safe Apnea Time (95% CI) was 283 (257-309) s in succinylcholine vs. 329 (303-356) s in rocuronium (P=0.01). The mean recovery period (95% CI) was 43 (39-48) s in succinylcholine vs. 36 (33-38) s in rocuronium (P=0.002). Blood gas analysis showed no difference between the two groups.
CONCLUSIONS: Succinylcholine was associated with a significantly more rapid desaturation and longer recovery of oxygen saturation than rocuronium during rapid sequence induction in overweight patients.

Desaturation following rapid sequence induction using succinylcholine vs. rocuronium in overweight patients
Acta Anaesthesiol Scand. 2011 Feb;55(2):203-8

Acute Med, All Updates, ICU, Resus

Furosemide infusion in acute decompensated heart failure

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A randomised controlled trial of 308 patients with acute decompensated heart failure compared continuous furosemide infusion with ‘low’ dose (equal to their total daily oral loop diuretic dose in furosemide equivalents) or high dose furosemide boluses. There was no outcome difference between infusion and bolus, although the high dose (2.5 times previous oral diuretic dose 12 hourly for 48 hours) improved patients’ symptoms while causing transient elevations in serum creatinine. Editorialist Dr G Fonarow states:
‘..these findings should change current practice. Since a high-dose regimen may relieve dyspnea more quickly without adverse effects on renal function, that regimen is preferable to a low-dose regimen. Administration of boluses may be more convenient than continuous infusion and equally effective.’
 

BACKGROUND: Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.
METHODS: In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients’ global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.
RESULTS: In the comparison of bolus with continuous infusion, there was no significant difference in patients’ global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients’ global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.
CONCLUSIONS: Among patients with acute decompensated heart failure, there were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).

Diuretic strategies in patients with acute decompensated heart failure
N Engl J Med. 2011 Mar 3;364(9):797-805

All Updates, Resus

Alfentanil for Procedural Sedation

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An evaluation of single-agent alfentanil for procedural sedation in the ED has been published by the team at Hennepin County Medical Centre. A short-acting opioid, alfentanil induces 7 to 9 minutes of pain relief after a single bolus of 10 mcg/kg, a duration of action similar to that of propofol. It produces analgesia and sedation but not amnesia. In this study of 148 adult patients, alfentanil doses and the use of supplemental oxygen were at treating physician discretion. it appeared to be effective for ED procedural sedation but displayed a rate of airway or respiratory events leading to an intervention similar to that of previous reports of deeper sedation with propofol. The authors state ‘Despite very high rates of procedural pain and recall, subjects remained highly satisfied.’

STUDY OBJECTIVE: We administer alfentanil sedation for minor procedures in the emergency department (ED), and our primary objective is to assess the incidence of airway and respiratory adverse events leading to an intervention. Our secondary goals are to assess for other adverse events, the depth and duration of sedation, the incidence of subclinical respiratory depression, and patient perceptions of the quality of the sedation.
METHODS: In this observational study of adults receiving alfentanil for ED procedures, we recorded the incidence of airway or respiratory adverse events leading to an intervention (increase/addition of supplemental oxygen, bag-valve-mask ventilation, airway repositioning, or stimulation to induce breathing). Secondary goals were assessed with monitoring (including capnography), the Observer’s Assessment of Alertness/Sedation (OAA/S) scale, and postprocedure patient visual analog scale ratings of pain, recall, and satisfaction.
RESULTS: Airway or respiratory events leading to intervention were observed in 39% of the 148 subjects (supplemental oxygen 18%, bag-valve mask 3%, airway repositioning 2%, stimulation 18%); none were clinically significant. The median OAA/S nadir was 4 (interquartile range 3 to 5). Median patient ratings were positive (pain 26 mm, recall 98, satisfaction 100 mm).
CONCLUSION: Alfentanil appears effective for ED procedural sedation but displays a rate of airway or respiratory events leading to an intervention similar to that of previous reports of deeper sedation with propofol.

Alfentanil for Procedural Sedation in the Emergency Department
Ann Emerg Med. 2011 Feb;57(2):117-21

All Updates, ICU, Resus

More on Rocuronium (and Sugammadex)

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While I am gradually being persuaded rocuronium might after all be a better choice than suxamethonium for rapid sequence intubation in critically ill patients- partly due to its relative preservation of apnoea time before desaturation in elective anaesthesia patients1 – I don’t believe that the existence and availability of its reversal agent, sugammadex, should really sway us in critical care. After all, we’re usually committed to getting an airway of some description (tracheal tube, supraglottic airway, or cricothyrotomy), and the relatively short duration of suxamethonium has never allowed me to ‘wake someone up and cancel the case’ in a critical care scenario. In fact, with sux, even healthy patients will desaturate before it wears off 2-4 if one is unable to intubate or ventilate.

But could we give sugammadex and reverse the rocuronium in time to save the patient in a can’t intubate/can’t ventilate (CICV) situation? This was tested in a simulation that studied the total time taken for anaesthetic teams to prepare and administer sugammadex from the time of their initial decision to use the drug5. The mean (SD) total time to administration of sugammadex was 6.7 (1.5) min, following which a further 2.2 min (giving a total 8.9 min) should be allowed to achieve a train-of-four ratio of 0.9. Four (22%) teams gave the correct dose, 10 (56%) teams gave a dose that was lower than recommended.
 
A reply to this article6 recommended some steps to speed up and improve the process:

  1. Brief the team that rocuronium is to be used and that should an unanticipated difficult airway situation be encountered, then sugammadex will be used to reverse the effects of the rocuronium.
  2. Allocate the task of drawing up the sugammadex to a specific team member who has no additional role in the rapid sequence induction.
  3. Before induction, a calculation is made of the dose of sugammadex (16 mg/kg) that would be required and the volume of drug that should be drawn up.
  4. The instruction is given that should the anaesthetist not confirm intubation within 2 min, then the sugammadex is to be drawn up and handed to the anaesthetist for administration.


There are of course rare situations where sugammadex can be a nuisance – it hangs around in renal failure and a recent case report 7described rocuronium (50mg followed by 30mg, patient weight not stated) failing to work on an elderly man who had received sugammadex 16 hours earlier! The authors of this case report state that in healthy patients, the mean cumulative percentage of sugammadex excreted in the urine over 24 h is 48–86%; therefore, a period of 24 h is recommended before a second administration of rocuronium. However, a good dose of rocuronium (1.2 mg/kg) should be effective after sugammadex reversal in previously healthy patients, but a study showed onset was slower and duration shorter if the second dose of rocuronium was given within 25 minutes of the sugammadex8.
So what are the take home points here? For me, the issues are:

  • Suxamethonium offers no real advantages over rocuronium for RSI in critical care – rocuronium at a dose of 1.2 mg/kg will provide similar intubating conditions to a good dose of sux9
  • Whatever you use, you need a rescue plan (supraglottic airway or transtracheal airway) for the CICV scenario
  • Sugammadex is a useful reversal agent in elective anaesthesia but is unlikely to be useful in a critical care scenario; however, if its use is anticipated it needs to be rehearsed as a standardised drill
  • Most of the literature on these agents pertains to well patients undergoing elective anaesthesia and we should be cautious about extrapolating results to the critical care setting
  • Finally, the urgency of a CICV can be reduced by CICVBCO – ‘can’t intubate, can’t ventilate, but CAN oxygenate’ – apnoeic diffusion oxygenation should be employed using pharyngeal or nasal oxygen10. Such a simple but underutilised technique can hugely improve the safety of RSI in critical care, and is described here.

1. Effect of suxamethonium vs rocuronium on onset of oxygen desaturation during apnoea following rapid sequence induction
Anaesthesia. 2010 Apr;65(4):358-61
2. Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine.
Anesthesiology. 1997 Oct;87(4):979-8
3. Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers.
Anesthesiology. 2001 May;94(5):754-9
4. Succinylcholine dosage and apnea-induced hemoglobin desaturation in patients
Anesthesiology. 2005 Jan;102(1):35-40
5. Can sugammadex save a patient in a simulated ‘cannot intubate, cannot ventilate’ situation?
Anaesthesia. 2010 Sep;65(9):936-41
6. Can sugammadex save a patient in a simulated ‘cannot intubate, cannot ventilate’ situation?
Anaesthesia. 2011 Mar;66(3):223-4
7. Unexpected failure of rocuronium-mediated neuromuscular blockade
Anaesthesia. 2011 Jan;66(1):58-9
8. Repeat dosing of rocuronium 1.2 mg kg−1 after reversal of neuromuscular block by sugammadex 4.0 mg kg−1 in anaesthetized healthy volunteers: a modelling-based pilot study
Br J Anaesth. 2010 Oct;105(4):487-92
9. Comparison of Succinylcholine and Rocuronium for First-attempt Intubation Success in the Emergency Department
Acad Emerg Med. 2011;18:11-14
10. Critical hemoglobin desaturation can be delayed by apneic diffusion oxygenation
Anesthesiology. 1999 Jan;90(1):332-3

All Updates, ICU, Resus

Neuromuscular blockade facilitates mask ventilation

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A blinded randomised controlled trial of rocuronium versus saline in anaesthetised patients demonstrated that mask ventilation was easier in paralysed patients.
The authors comment on the implications of this finding:
‘Our finding that neuromuscular blockade facilitates mask ventilation has important implications for the practice of managing difficult or impossible mask ventilation after administration of these drugs. Options in this case include returning to spontaneous ventilation, tracheal intubation, placement of a supraglottic airway device or obtaining emergency invasive airway access. In most cases, returning to spontaneous ventilation is not practical in a reasonable time frame, leaving tracheal intubation, supraglottic airway placement or emergency invasive airway access as the only feasible choices. Considerable evidence exists indicating that neuromuscular blockade facilitates tracheal intubation; and since our data further indicate that neuromuscular blockade facilitates mask ventilation, it follows that administering neuromuscular blockade is an advantage, rather than a hindrance when given early in a case of unrecognised difficult mask ventilation.‘
ABSTRACT
We wished to test the hypothesis that neuromuscular blockade facilitates mask ventilation. In order reliably and reproducibly to assess the efficiency of mask ventilation, we developed a novel grading scale (Warters scale), based on attempts to generate a standardised tidal volume. Following induction of general anaesthesia, a blinded anaesthesia provider assessed mask ventilation in 90 patients using our novel grading scale. The non-blinded anaesthesiologist then randomly administered rocuronium or normal saline. After 2 min, mask ventilation was reassessed by the blinded practitioner. Rocuronium significantly improved ventilation scores on the Warters scale (mean (SD) 2.3 (1.6) vs 1.2 (0.9), p<0.001). In a subgroup of patients with a baseline Warters scale value of >3 (i.e. difficult to mask ventilate; n=14), the ventilation scores also showed significant improvement (4.2 (1.2) vs 1.9 (1.0), p=0.0002). Saline administration had no effect on ventilation scores. Our data indicate that neuromuscular blockade facilitates mask ventilation. We discuss the implications of this finding for unexpected difficult airway management and for the practice of confirming adequate mask ventilation before the administration of neuromuscular blockade.
The effect of neuromuscular blockade on mask ventilation
Anaesthesia. 2011 Mar;66(3):163-7