Tag Archives: vasoactive drugs


Peripheral vasoactive infusions

periph-vasoactive-iconIt is often recommended that vasoactive agents are infused via central lines because of the risk of infiltration and tissue injury. The Children’s Hospital Boston transport team describe transport of 73 infants and children who were treated during interhospital transport with vasoactive medications via a peripheral intravenous line.

Median transport time was only 38 minutes (range 3[!!]-216) and median age was 1 (birth to 19) .

Dopamine monotherapy was given in 66 patients, adrenaline (epinephrine) monotherapy in 2, dobutamine plus phenylephrine in 1, dopamine and epinephrine in 3, and dopamine, dobutamine, and epinephrine in 1 patient.

In this retrospective study no patients developed infiltration or other complications related to peripheral vasoactive agents during interfacility transport. Eleven of the 73 patients, however, did develop infiltrates related to vasoactive infusion after arrival at the accepting institution; all infiltrates involved only minimal blanching and/or erythema, and all resolved without significant intervention and caused no lasting tissue injury. The risk of infiltration rose with increasing medication dose and duration of use.

Interesting that noradrenaline (norepinephrine) wasn’t used. This study is interesting but the overwhelming predominance of dopamine makes it hard to extrapolate this to European or Australasian practice.

The Use of Vasoactive Agents Via Peripheral Intravenous Access During Transport of Critically Ill Infants and Children
Pediatr Emerg Care. 2010 Aug;26(8):563-6

Terlipressin for refractory cardiac arrest in kids

Okay so it’s a small case series – but the results warrant further investigation: 10-20 mcg/kg terlipressin was given to five infants and children who arrested in the paediatric intensive care unit and who had not responded to several doses of adrenaline (epinephrine)1. Sustained return of spontaneous circulation (ROSC) was achieved in four, and two survived to be discharged home without sequelae and with good neurologic status at 6 and 12 month follow up. Interestingly, the four patients who had ROSC all had septic shock as the cause of their arrest. The two survivors had severe bradycardia and severe bradycarda-asystole as the arrest rhythms, and both received 20 mcg/kg terlipressin.

Terlipressin is a synthetic arginine vasopressin analog with a significantly longer duration of effect, which previously showed positive effects when administered to a small group of children unresponsive to prolonged resuscitative efforts2.

1. Pediatric cardiac arrest refractory to advanced life support: Is there a role for terlipressin?
Pediatr Crit Care Med. 2010 Jan;11(1):139-41

2. Beneficial effects of terlipressin in prolonged pediatric cardiopulmonary resuscitation: A case series.
Crit Care Med. 2007 Apr;35(4):1161-4

EGDT sepsis bundle challenged

An article in American Journal of Emergency Medicine by two intensivists challenges the science behind Rivers’ early goal-directed therapy (EGDT) protocol for severe sepsis / septic shock. In a nutshell:

  • Rivers’ study was small (n = 263), nonblinded, industry-supported and single-center
  • early fluids and antibiotics are a sound idea, but other components of EGDT are flawed
  • targeting a CVP is meaningless and could result in hypovolaemia or pulmonary oedema; dynamic markers of preload responsiveness such as pulse pressure variation or IVC diameter variation are better guides to fluid resuscitation
  • ScvO2 may be normal or elevated in septic shock patients; the low average ScvO2 in Rivers’ study has not been reproduced in subsequent studies.
  • packed cells have significant side effects and their non-deformability, pro-inflammatory and pro-thrombotic effects may impair microvascular perfusion and paradoxically worsen tissue oxygen delivery
  • dobutamine can potentially further worsen the haemodynamic status of patients with hypovolaemia, vasodilation, or a hyperdynamic circulation, which cannot be differentiated using CVP and ScvO2

Early goal-directed therapy: on terminal life support?
Am J Emerg Med. 2010 Feb;28(2):243-5

I like this paper, mainly because I have been uncomfortable with the chasing of arbitrary targets for some time. My own practice is to try to improve markers of organ hypoperfusion (such as lactate, urine output, mental status, and skin perfusion as well as blood pressure) by early antibiotics, fluid resuscitation guided by clinical and sonographic (IVC) signs, and vasoactive drugs guided by clinical and sonographic (basic echo) findings. I place a central venous catheter for access for the vasoactive drugs, rather than to get a CVP reading. I do measure ScvO2 with a central venous blood gas, but have rarely seen one below 70% even in severely shocked patients – I’m far more interested in clearing the lactate, as are these guys.

Lactate clearance goal in sepsis

Previous work in severe sepsis/septic shock patients has shown that a decrease in lactate concentration by at least 10% during emergency department resuscitation predicts survival. Since this is a potential alternative resuscitation goal to a central venous oxygen saturation (ScvO2) of 70% (as per surviving sepsis campaign guidelines), lactate clearance was compared with ScvO2 in a randomised non-inferiority trial of 300 patients.

All patients were managed in the ED and received fluids, antibiotics, and vasopressors as needed. Then lactate clearance or ScvO2 were measured, and if the respective goals of 10% or 70% were not met, packed cells or dobutamine were given depending on haematocrit. Lactate clearance was the percentage decrease in lactate between two venous specimens taken two hours apart.

Interestingly only 29 patients received either packed cells or dobutamine. Each group was similar in terms of time to antibiotic therapy and amount of fluid given. Patients in the group resuscitated to a lactate clearance of 10% or higher had 6% lower in-hospital mortality than those resuscitated to an ScvO2 of at least 70% (95% CI for this difference, –3% to 15%) exceeding the –10% predefined noninferiority threshold.

The authors conclude ‘these data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a computerized spectrophotometric catheter in the resuscitation of sepsis.’

Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial
JAMA. 2010 Feb 24;303(8):739-46

Noradrenaline vs Dopamine in Shock

Another nail in dopamine’s coffin? In a blinded randomised controlled trial in shocked patients1, there was no difference in mortality when dopamine was compared with noradrenaline as the initial vasopressor. However the dopamine group had a significantly higher incidence of dysrythmia. In addition, mortality was higher in the predefined subgroup of 280 patients with cardiogenic shock. The results of this European study of 1679 patients are very similar to those of a similar but open-label American trial in 252 patients published recently2.

1. Comparison of Dopamine and Norepinephrine in the Treatment of Shock
NEJM 2010;362(9):779-89

2. Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock
Shock. 2009 Oct 21. [Epub ahead of print]

Levosimendan in beta blocker overdose

Not a human study, but toxicology RCTS rarely are…

Levosimendan – a calcium sensitiser with inotropic properties, was superior to dobutamine and to saline placebo in the end points of survival, cardiac output, and mean arterial pressure in anaesthetised pigs with propranolol overdose.

Levosimendan as a Rescue Drug in Experimental Propranolol- Induced Myocardial Depression: A Randomized Study

Ann Emerg Med. 2009 Dec;54(6):811-817

Effect on noradrenaline on tissue oxygen delivery

Some persist in thinking and teaching that the ‘vasopressor’ noradrenaline (norepinephrine) increases mean arterial pressure (MAP) simply by increasing systemic vascular resistance, leading to concerns that it may increase blood pressure at the expense of tissue perfusion. This assertion is contested by many, who now have further support from this study.

In 16 patients with septic shock, various measures of peripheral perfusion were recorded while the dose of noradrenaline was increased to achieve target MAPs. The use of noradrenaline to achieve incremental targets for MAP was associated with increases in global oxygen delivery, cutaneous microvascular flow, and tissue oxygenation in patients with established septic shock; there were no associated changes in the preexisting abnormalities of sublingual microvascular flow. The authors state that these findings suggest that in patients with septic shock, improvements in global hemodynamics and tissue oxygen delivery can be achieved with noradrenaline, without exacerbating microcirculatory flow abnormalities.

The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock
Crit Care Med. 2009 Jun;37(6):1961-6

Neonatal prostaglandin E1 and apnoea

The risk of apnoea in neonates requiring prostaglandin E1 infusions for duct-dependent congenital heart disease is well described and often results in the recommendation to intubate prior to transfer. An American study of 202 transported infants on PGE1 shows a higher rate of transport-related complications in those that had been intubated. None of the 73 (36%) unintubated patients required intubation for apneoa during transport. These data are in keeping with a previous Australian study of 300 infants receiving PGE1 in which only 2 of 78 unintubated patients experienced apnoea.
To intubate or not to intubate? Transporting infants on prostaglandin E1
Pediatrics. 2009 Jan;123(1):e25-30