February 2, 2016

ICM ~ Article Review

Medical and surgical critically ill patients commonly experience pain. This occurs at rest and is also associated with routine care, procedural pain (1). Procedural pain remains a significant problem for many ICU patients, as evidenced from a recent large multinational study (2).  Notably however this data also suggested that patients who receive opioids for the management of procedural pain experience higher procedural pain intensity. Authors noted this could reflect that those receiving opioids for procedural pain were in more pain to start with, however it does raise questions as to whether specific opioids should be used to manage pain associated with routine procedures and also what the dose and timing of this dose should be in the critically unwell.  Little evidence explores this important question of the management of procedural pain in critically ill patients. In this paper, Robelda et al. aimed to address the question of whether a fentanyl bolus could be useful for analgesia to manage procedural pain.  

Robelda et al (3) conducted a single centre randomised, double blind, parallel group, placebo-controlled clinical trial to evaluate the effect of a single dose of pre-emptive fentanyl analgesia in reducing pain in adult mechanically ventilated ICU patients during turning.  Over a year period they block randomised 75 patients to receive either a one off bolus of fentanyl or placebo prior to two turning procedures, recognised to cause procedural pain.

Their primary aim was to compare the fentanyl with placebo groups with respect to incidence rates of pain (with the study being powered to detect a 20% decrease in pain incidence on turning in the fentanyl group) and also a reduction in overall pain during the study period.  Their secondary aim was to evaluate the safety of a one off fentanyl bolus in these patients.

The fentanyl dose was calculated based on 1 microgram/kg for medical patients or 1.5 microgram/kg for surgical patients, using either ideal or actual body weight whichever gave the lower dose, with a ceiling absolute dose of 100 micrograms and the median dose given being 70 micrograms (range 58-100). Drug concealment occurred in the pharmacy with both drugs being identical to clinical staff administering them. All other regular care including analgesia and sedation was continued throughout the study. 

Pain was assessed by one investigator for all study patients using the behavioural pain scale (BPS), recommended for use in critical illness in patients unable to self report pain (1).  Pain was assessed at 6 predetermined time periods during the study and these BPS values were then used to reflect the magnitude of changes in pain behaviour over time. Demographic and clinical data were collected from medical records. All data underwent an intention to treat analysis.  

Main findings 

1.    57% of all patients had pain (BPS>3) and 17% had significant pain (BPS>5) at baseline.  
2.    Despite there being no significant difference between median pain scores between the groups during turning, there was a reduction in the incidence of pain (74% versus 94% of patients had a BPS of >3), with a NNT of 5. 
3.    A non-statistically significant difference in the patients experiencing significant pain (BPS>5) was present (49% vs 64%).  
4.    Notably the magnitude of pain, as measured by AUC of BPS throughout the study period was statistically significantly different, being lower in the fentanyl group (p=0.016).
5.    Despite there being no overall difference in adverse events between the groups, all of the cases of respiratory depression occurred in the fentanyl group highlighting an important risk in administrating a bolus of fentanyl.   

The findings at first look seem to support the use of a one off bolus of fentanyl for procedural pain in mechanically ventilated ICU patients as it appears to be effective in reducing both the overall incidence of pain associated with turning and also reducing the magnitude over time of pain.  

Points for discussion
Proportion of patients developing severe pain (BPS>5) at time of turning and pain was 49%. Therefore, whilst the results appear statistically significant, in real clinical terms, this fentanyl regimen is unlikely to adequately manage pain associated with turning. 

A high proportion of patients were in pain prior to turning, despite 90% of patients being treated with opioid infusions, and adherence to clinical pain management protocols. This emphasises the need for better overall management of pain on the ICU and the development of effective regimens and protocols to aid clinical staff. The intervention may have been addressing background, rather than procedural pain. 

The difference in incidence of pain at 30 minutes post turning should also highlight to clinicians that a simple procedure such as turning can have a long lasting analgesic requirement and that agents used to combat procedural pain need to mirror this time course. 

The study also draws a distinction between medical and surgical ICU patients. However, this distinction may not be appropriate as there is growing evidence that medical patients have high rates of unrecognised pain and are often undertreated (4). 

Concluding Remarks
The authors should be congratulated for exploring an area with such a paucity of evidence and they did show some small effect from the intervention. The authors rightly suggest their work advances the small amount of knowledge regarding management of procedural pain and supports the concept that a dynamic analgesic regimen should be used to deal with procedural pain. What still remains to be discovered is the optimal drug, dose and timing.

This article review was prepared and submitted by Harriet Wordsworth, Helen Laycock (ESICM Journal Review Club members) and Brijesh Patel (NEXT committee member).


1.    Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. 2013. pp. 263–306.
2.    Puntillo KA, Max A, Timsit J-F, Vignoud L, Chanques G, Robleda G, et al. Determinants of procedural pain intensity in the intensive care unit. The Europain® study. Am J Respir Crit Care Med. 2014 Jan 1;189(1):39–47.
3.    Robleda G, Roche-Campo F, Sendra M-À, Navarro M, Castillo A, Rodríguez-Arias A, et al. Fentanyl as pre-emptive treatment of pain associated with turning mechanically ventilated patients: a randomised controlled feasibility study. Intensive Care Medicine. 2016 Feb;42(2):183–91.
4.    Chanques G, Sebbane M, Barbotte E, Viel E, Eledjam J-J, Jaber S. A prospective study of pain at rest: incidence and characteristics of an unrecognized symptom in surgical and trauma versus medical intensive care unit patients. Anesthesiology. 2007 Nov;107(5):858–60.

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