it is a potent opioid analgesic with ultra - short duration of action , extremely rapid peak effect , and an equally consistent and rapid elimination with complete cessation of effect within a maximum of 10 minutes . in clinical practice
an excessive bolus dose however can cause rapid onset of potentially life - threatening side effects , such as bradycardia , hypotension , muscular rigidity , and apnea .
we report a case of an inadvertent remifentanil bolus which induced sudden bradycadia , hypotension , and apnea .
it was immediately detected and successfully managed in our surgical intensive care unit ( sicu ) .
a 36-year - old woman was admitted to sicu after resection of a hepatic mass .
she was intubated , ventilated , and sedated with propofol and remifentanil infusion provided analgesia . on the second postoperative day
she remained hemodynamically stable , was weaned from the ventilator , and extubated on day 4 .
propofol and remifentanil infusions were stopped 1 hour and 15 minutes before the extubation , respectively .
after tracheal extubation , the patient was fully awake , breathing spontaneously , respiratory rate was 20 - 24 breaths per minute , oxygen saturation was 100% , and she was hemodynamically stable .
thirty minutes after extubation , the lumen of the central venous catheter , used for the remifentanil infusion up to 15 minutes prior to extubation , was used to infuse a plasma protein fraction bag at a rate 125 ml / hour . within 2 - 3 minutes
, the heart rate of the patient decreased to 48 beats per minute , oxygen saturation dropped to 60% , she stopped breathing , and systolic blood pressure decreased to 86 mm of hg [ figure 1 ] .
atropine was given , and within 3 minutes her heart rate increased to 60 beats per minute and her blood pressure improved to 108 mm of hg .
concurrently , her heart rate and blood pressure improved ( 72 - 74 beats per minute and 112 - 120 mm of hg , respectively ) oxygen saturation reached 100% with a respiratory rate of 22 - 24 breaths per minute ( oxygen supplementation 5 liters per minute was given by nasal canula ) .
remifentanil is an ultra - short acting opioid analgesic which acts on mu - receptors ; it has a rapid onset of action ( 1.3 minutes ) .
this combined with an ultra - short duration of action and rapid elimination ( 3 minutes ) makes remifentanil an analgesic medication of choice in icus .
if an excessive remifentanil bolus dose is injected , it leads to potentially life - threatening adverse effects such as bradycardia , hypotension , muscular rigidity , and apnea .
the use of remifentanil for patient - controlled analgesia ( pca ) , in which the bolus dose of remifentanil range between 0.25 and 1 g / kg has been described .
remifentanil - pca was provided with a bolus facility of 50 pg administered over 5 minutes , followed by a 5-min lockout in combination with a background infusion .
bowdle et al . studied the effects of remifentanil in the immediate postoperative period ; 29% patients developed respiratory adverse events .
interestingly , apnea occurred in 8.7% patients and 83% of them received a bolus dose of remifentanil . in this study ,
depending on the type of tubing used and the site of connection , the dead space of the main intravenous tubing between the port where remifentanil is inserted into the main intravenous infusion line and the patient 's vein can vary from 1 to 5 ml . in these conditions , a change in the flow rate of the intravenous fluid will have a clear impact on the delivery of remifentanil .
if the flow in the main intravenous tubing is suddenly increased , the amount of remifentanil contained in the dead space will be flushed abruptly into the patient 's circulation , leading to a bolus effect of remifentanil mainly bradycardia , hypotension , apnea , and rigidity . in our patient ,
remifentanil was used in a standard solution of 400 g / ml . as the patient was on higher dose ( 0.4 mcg / kg / minute ) of remifentanil
1 - 2 ml may have remained in the tubing and bivalve connection must have been flushed when the same port and connection were used to infuse the plasma protein fraction with higher rate ( 125 ml / hour ) .
the bolus dose of the remifentanil flushed must have been around 400 - 800 g .
this is sufficient to cause the potentially life - threatening adverse effects encountered in this patient .
bowdle et al . have also reported a case of one patient becoming unconscious , cyanosed , and bradycardic after an intravenous line was flushed ; the same line was used for remifentanil infusion . to avoid such serious preventable clinical problems ,
hug has suggested ventilation with a bag - valve - mask and following recommendations . 

avoid intravenous bolus and flushing of the line which was used for remifentanil infusion.treat and/or prevent bradycardia and hypotension with anti - cholinergic medications.if apnea and rigidity occur with excessive bolus of remifentanil , it will be difficult to give positive pressure ventilation .
in this situation , a short - acting muscle relaxant can be used and the patient ventilated until the effects of the bolus dose wear off . 
  avoid intravenous bolus and flushing of the line which was used for remifentanil infusion . treat and/or prevent bradycardia and hypotension with anti - cholinergic medications .
if apnea and rigidity occur with excessive bolus of remifentanil , it will be difficult to give positive pressure ventilation .
in this situation , a short - acting muscle relaxant can be used and the patient ventilated until the effects of the bolus dose wear off . to prevent similar incidents in our icu in future
, we started to use a more diluted remifentanil infusion , given through a dedicated cannula or connecting remifentanil infusion closer to the patient using a three way , and started to remove the infusion lines used , to place the remifentanil on hold for preparing the patient for extubation .
it is essential to be aware of these rapidly occurring , potentially life - threatening effects of excessive bolus doses of remifentanil .
acute care physicians , intensivists , anesthesiologists , and critical care nurses must be aware of this to ensure proper management .
 remifentanil is an opioid analgesic frequently used in intensive care patients because of its rapid onset of action , potency , and ultra - short duration . 
 if an excessive dose is given , it leads to rapid , short lasting , potentially life - threatening side effects such as apnea , bradycadia , hypotension , and rigidity , following rapid peak serum levels . we report a 36-year - old woman developing apnea with bradycardia and hypotension , following an infusion in the central venous catheter lumen that had been used for remifentanil till tracheal extubation . 
 the patient was immediately ventilated with bag - valve - mask and improved within 8 minutes . 
 she became fully awake , heart rate and blood pressure returned to normal , and oxygen saturation improved to 100% . 
 acute care physicians , intensivists , anesthesiologists , and critical care nurses should be aware of this clinical problem in order prevent it as much as possible and to initiate immediate resuscitative measures . 
Introduction
Case Report
Discussion