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HIGH ALERT Medication Feature: Reducing Patient Harm from Opiates

In our January 11, 2007 newsletter, we announced our 2007 New Year's resolution to highlight for our readers key information about selected high-alert medications and how to reduce patient harm when prescribing, dispensing, and administering these drugs. We began this yearlong effort with a feature on anticoagulants; we continue in this issue with a focus on opiates. 

An opiate (morphine) was among six medications on the very first list of high-alert medications published by ISMP in 1989.1 According to data from the USP-ISMP Medication Errors Reporting Program and USP MEDMARX, opiates, particularly morphine and hydromorphone, are still among the most frequent high-alert medications to cause patient harm.2 In our 2003 survey about high-alert medications in acute care settings, IV opiates were also among the top ten medications/ class of medications considered to be 'high-alert.' The Institute for Healthcare Improvement has also reinforced the need for a nationwide effort to reduce patient harm when using opiates, making this class of drugs one of four medications on which to focus its 5 Million Lives Campaign.

Errors with opiates have led to serious adverse events, including allergic reactions, failure to control pain, over-sedation, respiratory depression, seizures, and death. Listed below are some of the error-related risks associated with opiates (IV, epidural, transdermal, transmucosal, oral liquid concentrates, immediate/sustained release) that have been reported in our newsletters or learned from root cause analyses of actual errors. Suggested safeguards follow in a checklist format. Although vitally important, advanced technologies such as computerized prescriber order entry (CPOE), bar-coding, and smart pumps have not been included, nor have broad-based error-reduction strategies, such as medication reconciliation, so that more drug-specific interventions can be provided.       

Common Risks Associated with Opiates

Look-alike drug names and packages

  • Mix-ups between hydromorphone and morphine, caused at times from the misconception that hydromorphone is the generic name for morphine.
  • Mix-ups between paregoric (camphorated tincture of opium) and tincture of opium (which contains 25 times more morphine).
  • Selection of the wrong product due to look-alike names or packaging of prefilled syringes, vials, ampuls, and minibags of various opiates.

Dosing errors

  • Misprogramming of infusion pumps used to deliver opiates.
  • Delivering bolus doses by increasing the pump infusion rate and forgetting to change it back to the correct rate.
  • Prescribing initial doses too high for opiate-naïve patients, especially with hydromorphone and fentanyl patches.
  • Use of a basal rate of infusion for opiate-naïve patients during the delivery of patient controlled analgesia (PCA).
  • Unfamiliarity with proper oral-to-IV dose conversions for some opiates.
  • Prescribing short-acting opiates without knowledge that long-acting morphine (DepoDur) has been administered; prescribing opiates for patients who have received an epidural opiate without knowledge.
  • Failure to remove the old fentanyl patch before applying a new patch.
  • Oversedation of patients caused by delivery of PCA doses by nurses or family members rather than the patient (i.e., PCA by proxy).

Concentration errors

  • Confusion between concentrated forms of oral liquid morphine and the standard solution, especially if both are available as unit stock.
  • Administering overdoses of oral liquid morphine if physicians prescribe the medication by volume rather than by metric weight and nurses use the more concentrated form to prepare the dose.
  • Selecting the wrong concentration of opiates from among various concentrations available (e.g., 5 mg/mL instead of 1 mg/mL concentration of morphine for PCA use).

Use of dangerous abbreviations

  • Confusion with the meaning of DTO (deodorized tincture of opium, or diluted opium tincture [1:25]).
  • Confusion between MSO4 (morphine sulfate) and MgSO4 (magnesium sulfate).

Line confusion

  • Confusion between an IV and epidural infusion line leading to errors in the route of administration of an opiate.

Adverse drug reactions

  • Allergic reactions to opiates.
  • Meperidine use in elderly patients or patients with renal compromise, leading to toxic levels of normeperidine, a meperidine metabolite, which may cause irritability, nervousness, agitation, tremors, and seizures.

Mislabeled syringes

  • Diluting morphine using a saline flush syringe and then withdrawing the medication back into the syringe, which is still labeled as a saline flush, not morphine.

Patient monitoring problems

  • Failure to notice respiratory depression due to insufficient, improper, or untimely monitoring of patients receiving opiates.

Unintended use

  • Unsecured storage or disposal of fentanyl patches, leading to drug diversion or accidental application by young children on their own bodies.

Recommended Safety Improvements

Use constraints

  • Limit oral liquid opiates in unit stock to conventional concentrations, except in chronic pain and oncology units.
  • Dispense concentrated oral liquid opiates from the pharmacy if required for a specific patient and return unused supply to the pharmacy upon patient discharge.
  • Provide all oral liquid opiates in unit-of-use packaging or patient specific unit doses in oral syringes (no bulk bottles).
  • Limit unit stock of fentanyl patches to 25 mcg/hour.
  • Avoid the use of meperidine for pain control, especially in elderly and renal-compromised patients; limit its availability outside the pharmacy and remove it from preprinted orders.
  • Avoid the use of basal rates with PCA for pain control of an opiate-naïve patient.
  • Consider deleting paregoric and opium tincture from the formulary; if one or both drugs remain on the formulary, dispense   the products from the pharmacy (not stocked on units or in automated dispensing cabinets [ADCs]).
  • Prepare all opiate infusions in the pharmacy if admixture is required.
  • When appropriate, use non-opiate medications and non-pharmacologic therapies for pain.
  • For CPOE systems, list only the recommended medications, strengths, and doses on pain control order sets.
  • Limit the ability to obtain opiates via override from an ADC or from unit stock before a pharmacist has reviewed the order.
  • Separate morphine and hydromorphone, and concentrated and conventional strengths of oral liquid opiates. 

Improve access to information

  • Include the brand name Dilaudid with hydromorphone in orders, labels, computer screens, and medication administration records (MARs).
  • Provide equianalgesic charts for oral-to-IV conversions for prescribers and nurses.
  • Require documentation of patch application (including location) and removal on MARs.
  • Establish dose ranges for opiates by weight, and build dose alerts in the order entry system. Include maximum doses on preprinted orders for prn opiates.
  • Consult a pain management specialist for high-risk patients (e.g., the elderly, patients on concentrated opiates, epidural analgesia).
  • Build reliable systems for communicating opiates delivered before, during, and immediately after an invasive/surgical procedure. 
  • Build alerts in the computer system to warn if opiates are prescribed within a specified time of receiving long-acting morphine.

Simplify and standardize

  • Establish protocols for pain management, including a standard pain scale for assessment, guidelines for the use of specific analgesics, standard order forms/screens, conditions requiring a dose reduction, and requirements for monitoring. 
  • Establish protocols for moderate sedation, including dosing and monitoring guidelines.
  • Establish patient selection criteria, protocols, and preprinted orders for PCA. Include maximum bolus, demand, and lock-out doses and monitoring guidelines.
  • Administer bolus doses from pharmacy dispensed syringes, not from infusion bags.
  • Reduce the variety of opiates and other analgesics prescribed for patients on protocols and various standard order sets.
  • Prescribe and dispense liquid medications with the dose specified in milligrams.
  • Standardize to a single drug (e.g., morphine) as the opiate of choice for PCA.
  • Prohibit the abbreviations DTO, MSO4, and MGSO4. 


  • Stock morphine and hydromorphone in different strengths (e.g., 1 mL prefilled syringes of hydromorphone 1 mg/1 mL; 2 mL prefilled syringes of morphine 2 mg/mL).
  • Use tall-man lettering for HYDROmorphone on labels, MARs, and drug listings on computer screens (including ADCs).
  • Change vendors or apply auxiliary warning labels to storage bins of opiates, and products when appropriate, that look similar to help differentiate them.
  • Use different infusion pumps for epidural and IV infusions, and special yellow-striped tubing without ports for epidural infusions.

Use reminders

  • Label the distal ends of all access lines to distinguish IV from epidural lines.
  • Apply warning labels to concentrated forms of morphine and opium tincture, and build computer screen alerts to remind staff about their concentration.

Employ redundancies

  • Require independent double checks of the patient, medication order, and appropriateness of the drug, dose, pump settings, and line placement for opiate infusions.

Monitor patients

  • Establish guidelines for appropriate monitoring of patients who are receiving opiates, including frequent assessment of the quality of respirations (not just a respiratory rate) and specific signs of oversedation. Ensure resources (personnel and equipment) are available to monitor patients per established guidelines. Use standardized formats for documenting pain control and monitoring values.
  • Establish protocols for reversal agents that can be administered without additional physician orders when warranted.
  • Ensure that oxygen and naloxone are available where opiates are administered.
  • If providing nurse-delivered PCA to confused adults or young children, establish strict requirements for enhanced observation and monitoring.
  • Do not rely on pulse oximetry readings alone to detect opiate toxicity. Use capnography to detect respiratory changes caused by opiates, especially for patients who are at high risk (e.g., patients with sleep apnea, obese patients).

Educate patients       

  • Administer opiates to reach a pain score mutually agreed upon by patient and clinicians prior to procedures to avoid unrealistic expectations of no pain and reduce the risk of over-sedation.
  • Instruct patients who use fentanyl patches to apply them properly, avoid heat exposure, and to store and dispose of the patches in a secure manner to avoid unintended access by children, pets, or drug-seeking individuals.
  • Educate patients and families about PCA preoperatively, preferably before admission when patients are alert, not after they have received anesthesia. Teach patients how to use PCA, and warn against dosing by proxy.


  1. Davis NM, Cohen MR. Today’s poisons: how to keep them from killing your patients. Nursing 89. January 1989;49-51.
  2. Smetzer J, Cohen MR. Medication error reporting systems. In Medication errors, 2nd edition. Cohen, MR ed., 2007: 511-548; American Pharmaceutical Association, Washington, DC.