Dept Of Anesthesiology & Critical Care, University Of Pennsylvania School Of Medicine

What is six sigma? How does it apply to health care?

There are two meanings 1) Sigma ( σ ) is the accepted symbol for 1 standard deviation from the mean of the “normal” distribution (bell curve).  Since 1 sigma would exclude 31.8% of a normally distributed event under consideration and three sigma would exclude 0.3%, six sigma implies events of very low frequency (on the order of 3 per million). 2) Six sigma is also commonly used as the name of a process of quality control originally developed at Motorola Corporation and later adopted by many including General Electric Company (a six sigma error rate is considered to be virtually flawless).  In many industries application of the methodology has reduced defects, improved customer satisfaction, and decreased costs.  With respect to medicine, Parker et al used these techniques to develop a process that improved adherence for antibiotic prophylaxis in patients undergoing cardiac surgery (1); Women and Children’s hospital of Charleston used six sigma to enhance access to care by decreasing time to appointment and waiting time to see a doctor, increase patient satisfaction, and improve revenues in a resident run obstetrics and gynecology clinic (2); and Massachusetts General Hospital avoided the addition of an additional shift for its proton beam facility by changing how it scheduled cases requiring anesthesiologists (3).  Key to the success of this methodology is the fact that it is data driven.  It focuses on process improvement and variation reduction using the paradigm of define, measure, analyze, improve, and control (4).  It can be applied to both existing and planned processes.  We do not like to consider our practice of medicine to be the same as manufacturing super soaker recreational water guns.  However for success both require the correct application of a sequence of steps.  In the case of medicine  failure of any one of those steps may lead to patient injury, patient or family dissatisfaction or increased costs in the form of a cancelled case, increased hospital stay, etc.

1)      Parker BM et al: Six sigma methodology can be used to improve adherence for antibiotic prophylaxis in patients undergoing cardiac surgery.  Anesth Analg 2997:104:140-6

2)      Calhoun BC: Six-sigma inspired workflow redesign enhances access to care and increases patient satisfaction, visits, and revenues in obstetrics and gynecology residency clinic.  (http://www.innovations.ahrq.gov/content.aspx?id=1868 )

3)      Krasner J: New medicine for what ails hospitals.  Boston Globe January 28, 2008 (http://www.boston.com/business/healthcare/articles/2008/01/28/new_medicine_for_what_ails_hospitals? )

4)      Sivy J: Six Sigma.  Carnegie Mellon Software Engineering Institute Software Technology Roadmap (http://www.sei.cmu.edu/str/descriptions/sigma6_body.html )

David S. Smith, M.D., Ph.D.

Anoxic Encephalopathy; anesthesiologists still involved

The Pennsylvania Patient Safety Authority summarizes 3 years of submitted reports related to anoxic encephalopathy in Pennsylvania Hospitals (http://www.psa.state.pa.us/psa/lib/psa/advisories/v5n1march_2008/mar_2008_v5_n1.pdf ), pages 34 - 35.  Thirty one reports were identified.  Seventeen of the 31 patients died.  Nineteen appeared to be associated with the perioperative period with 4 occurring in the OR.  The PSA emphasizes that anoxic encephalopathy can be associated with more then just airway and ventilation; three occurred in association with blood loss.  The following causes were noted: BIPAP came off, arrest following sedation on the floor, arrest during OR intubation, arrest on induction of anesthesia, post extubation arrest at the end of operation, arrest following sedation in MRI, difficult reintubation in an ICU, and propofol syndrome, among others.  Eight of the 31 incidents were related, in some way, to airway management.  When one considers the total number of patients cared for in Pennsylvania hospitals during this time period, the incidence is very low, however each one had a devastating effect on the families of these patients and most likely on the caregivers involved.  Dr. Fleisher notes that “while some have argued that we approach six sigma in terms of cardiac arrests and deaths directly due to medical error, we must continue to learn from these events in order to provide the best possible care for our patients.”

David S. Smith, M.D., Ph.D.

Dr. Fleisher is Chair of Anesthesiology and Critical Care, University of Pennsylvania

There is an increased methadone use for pain therapy; there is a marked increase in methadone related deaths. Are they related?

According to one of my pain therapy sources, methadone, which is longer acting and does not cause euphoria compared to other narcotics, is increasingly being used for the treatment of chronic pain.”  However there now appears to be an increase death associated with methadone use.  According to a recent Philadelphia Inquirer article (April 18, 2008), death of people taking methadone is increasing at a very rapid rate.  According to the National Center for Health Statistics the number of methadone deaths across the United States rose from 786 in 1999 to 4,462 in 2005.The Inquirer notes that the drug is easily diverted to the black market.  They state that even though methadone does not produce a “high” it is often combined with other drugs.

            Methadone has been recently associated with cardiac death in patients using this drug.  Chugh et al (1) over a four year period prospectively evaluated all patients who had sudden cardiac death and underwent investigation by the medical examiner in the metropolitan area of Portland.  Case subjects had a therapeutic blood level of methadone and these were compared to patients with no identified methadone.  Patients with recreational drug use or any drug overdose were excluded.  They found a total of 22 sudden cardiac death cases with therapeutic levels of methadone.  The most common indication for methadone use was pain control.  They found that significantly fewer of the patients taking methadone had a structural abnormality that would explain the cardiac death compared to the non methadone group.  They speculated that death in the methadone cases may have been related to an arrhythmia.  Others (2) have suggested that methadone may produce potassium ion channel blockade, prolonged QT interval and the potential for a Torsade de Pointes arrhythmia.

            The UPENN chief of pain medicine provides the following additional information: most experts believe that methadone-related deaths are attributable to 2 main issues.  First, methadone is used by relatively inexperienced clinicians who do not understand proper dosing.  In these patients, either the initial dose is too high, or dose changes are made too frequently, and the patient "over shoots" the proper dose and then experiences opioid-induced respiratory compromise.  Second is the rarer risk of Torsade de Pointes.  This appears to be an adverse event unique to methadone among the potent opioids.  Methadone appears to block the rapid component of the delayed rectifier potassium current in a dose-dependent fashion, and as a result may prolong the QT interval.  This effect is most commonly observed in patients taking high-dose methadone (> 100 mg/day), but has been reported at lower doses.  The good news is that QTc intervals of 500 msec or more are predictive of an increased risk for Torsade de Pointes.  One of our pain doctors obtains an ECG on patients on methadone if their daily dose is > 80 mg.

            With respect to methadone there is a large inter-individual variability and that reaching a steady state can take 7 days or more.

1)      Chugh SS et al: A community based evaluation of sudden death associated with therapeutic levels of methadone.  Am J Med 2008;121:66-71

2)      Maremmani I et al: QTc interval prolongation in patients on long-term methadone maintenance therapy.  Eur Addict Res 2005;11:44-49

David S. Smith, M.D., Ph.D.

An argument for NOT stopping antiplatelet drugs prior to surgery

The Anesthesia Pain Service Guidelines presented earlier call for stopping clopidogrel seven days prior to surgery if neuraxial anesthesia is desired.  It is important to note, however, there have been a number of reported cases of coronary artery occlusion in patients with drug eluting stents after temporary cessation of either aspirin or clopidogrel.  Bengeri (1) and Bolsin et al (2) argue that the risks of cessation outweigh the risk of increased surgical bleeding and that these antiplatelet drugs should be continued into the perioperative period.  Bolsin notes that they surveyed 24 patients with drug eluting stents who presented for a total of 43 non-cardiac surgery procedures.  On 15 occasions clopidogrel was stopped though aspirin was continued.  Three patients experienced myocardial infarction secondary to in-stent thrombosis.  Two of the three infarcts occurred prior to surgery.  Only one patient of the 24 experienced excessive bleeding.

            The American College of Cardiology/American Heart Association joint guidelines for reducing the risk of a perioperative cardiac event (3) emphasized the need to continue anti-platelet drugs perioperatively.  The cases presented by Bengeri and by Bolsin et al together with the recommendations found in the ACC/AHA guidelines force the conclusion that antiplatelet drugs should not be discontinued prior to surgery in patients receiving these drugs after coronary stenting.  The Anesthesia Pain Service notes that epidural analgesia can be safely provided to patients taking aspirin.  In patients on clopidogrel, the drug should be continued preoperatively but epidural analgesia should not be offered.

1)      Bengeri S: Successful management of patients with a drug-eluting coronary stent presenting for elective surgery (letter).  BJA 2007;98:841-8

2)      Bolsin S et al: Comment on Bengeri 2007 (letter): BJA 2007;98:842

3)      Fleisher LA et al: ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for non cardiac surgery. http://circ.ahajournals.org

David S. Smith, M.D., Ph.D.

Package insert warnings for anti platelet or anticoagulant drugs

The package insert for Lovenox brand enoxaparin contains a black box warning about the association of this drug and hematomas after spinal or epidural anesthesia.  They note that the risk is increased by the presence of indwelling epidural catheters for analgesia, the presence of additional drugs that affect hemostasis such as NSAIDS or platelet inhibitors, and traumatic or repeated spinal or epidural puncture.  The package insert for Plavix brand clopidogrel contains no specific warnings about the concomitant use of this drug and regional anesthesia however it does warn that if a patient is to undergo elective surgery and an antiplatelet effect is not desired than clopidogrel should be discontinued five days prior to the procedure.

David S. Smith, M.D., Ph.D.

Orthopedic surgery, DVT prophylaxis and regional anesthesia

Orthopedic surgery is associated with a high incidence of thromboembolism and orthopedic surgeons have been among the most aggressive with respect to DVT prophylaxis.  Traditionally anesthesiologists have viewed many orthopedic surgery procedures as “perfect” for regional techniques such as spinal or epidural anesthesia.  Rowlingson et al is optimistic about the continued use of regional anesthesia in orthopedic patients who are receiving LMWH.  They note that “the key to optimizing patient safety however, depends on a careful calibration of the total daily dose and the timing of the first and subsequent doses of LMWH with the timing and management of the regional anesthetic procedure.”  I am not convinced that this degree of coordination and cooperation is possible particularly given the consequences (paralysis).  Dr. Richman at Penn Presbyterian Medical Center notes that most of their orthopedic surgeons use LMWH for post operative DVT prophylaxis and that patients receiving LMWH never get epidural anesthesia.  For knee surgery the anesthesiologists are using femoral nerve catheters sometime in combination with PCA.  They are willing to do spinal anesthesia as long the LMWH is not started until after surgery.  He notes that most of their orthopedic surgery patients receive general anesthesia (personal communication).

            

REF: Rowlingson JC, Hanson PB: Neuraxial anesthesia and low-molecular-weight heparin prophylaxis in major orthopedic surgery in the wake of the latest American Society of Regional Anesthesia Guidelines.  Anesth Analg 2005;100:1482-8

David S. Smith, M.D., Ph.D.

Heparin contamination -- newest findings

A series of adverse anaphylactic like reactions, mostly in dialysis patients, led to recall of Baxter Pharmaceutical brand Heparin in January, 2008.  Raw material for this heparin was sourced in China and a contaminate was suspected.  Baxter is the source for about half of the heparin used in the United States.  A supply loss of this magnitude is serious considering the ubiquity of heparin use.  Two papers from overlapping groups of investigators have used complex chemical techniques to identify the contaminate (an oversulfated chondroitin sulfate, not found in nature) and have linked this contaminate to direct activation of the kinin-kallikrein pathway in human plasma and the potential production of bradykinin, a potent vasoactive mediator.  This contaminate also generates C3a and C5a which are potent vasoactive mediators.

            Of particular interest is the speed of investigation and publication.  The first notification from the Centers for Disease Control of a potential problem was January 7, 2008.  The Heparin recall is dated January 17 and the research described above was done, the papers written, accepted and available online about 14 weeks later.  Clearly the nearly 29 investigators listed as authors, in roughly 8 laboratories made this work their first priority.

            Considering the nature of the contaminate and the fact that the authors have proposed screening techniques it is unlikely that this particular contaminate will re-occur however certain lesions can be learned.  1) The importance of reporting adverse or unexpected reactions to the FDA Medwatch web site (http://www.fda.gov/medwatch/ ).  The initial reports related to heparin came from the Missouri Department of Health to the FDA.  2) Be alert to unusual responses to medications.  The symptoms that occurred are not typical for heparin (hypotension, generalized sensations of warmth, numbness or tingling in the extremities, shortness of breath, chest tightness, and nausea.  3) Be prepared to treat the unexpected.  Though most patients recovered with cessation of the Heparin there may be as many as 103 deaths.

1)      Guerrini M et al: Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events.  Nature Biotechnology.  April 23, 2008 Advance online publication DOI 10.1038/nbt1407

2)      Kishimoto TK et al: Contaminated heparin associated with adverse clinical events and activation of the contact system.  NEJM April 23, 2008 Published on line DOI 10.1056/NEJMoa0803200

3)      MMWR: Acute allergic-type reactions among patients undergoing hemodialysis – multiple states 2007 – 2008.  MMWR Weekly 2008;57:124-125

            4)   Perrone M: FDA probes deaths from contaminated heparin.  Charleston Gazette. April 9, 2008

David S. Smith, M.D., Ph.D.

Intraoperative awareness - potential causes and decreasing the risk

AIMS is a large, anonymous, multicenter, reporting system of anesthesia incidents that is in widespread use in Australia and parts of Asia.  Bergman et al examined the data base when there were 8372 abstracted reports collected between 1988 and 2001.  The authors queried on the keyword “awareness.”  Using specific definitions of awareness they found 81 reports of which there were 50 cases of definite awareness and 31 with a high probability of awareness.  They could find no obvious cause for awareness in 13 (16%) of the cases. Low inspired volatile agent concentration appeared to be responsible for 36 (44%) of the 81 cases.  In 14 of these cases there was no agent monitor present.  Five of these cases appeared to be due to prolonged attempts at intubation and four cases were due to reducing delivered anesthetic secondary to hypotension or cardiovascular instability.  Thirty two cases were due to inadvertent paralysis of an awake patient.  Case review suggested that inattention or distraction were contributory in 20 cases, haste in 14 and fatigue in 5.

            This study covers a later period than did the closed claims analysis study of awareness (Domino KM et al: Anesthesiology 1999;90:053-61).  In my opinion, at least in the United States, the 1988 – 2001 period is reasonably similar to current practice yet awake paralysis persists and in Bergman et al awake paralysis was the most common cause for awareness.  Picking up the wrong syringe (a paralytic instead of the desired drug) was a recurrent cause of awareness.  Keeping syringes of paralytic drugs away from other drugs might help reduce this problem.  The authors expressed particular concern about the incidents of awareness with no apparent cause.   Two of the 13 cases had agent analyzers and apparently adequate doses of volatile agent.  Two cases occurred during ECT when no volatile agent is typically used.

            Neither this study nor the closed claims study allows calculation of incidence since the total number of cases from which these reports are drawn is not known.  In addition reporting is voluntary and the threshold for reporting most likely varied from practitioner to practitioner.  Finally if patient report was the major source of information then there was most likely underreporting as most patients do not volunteer awareness information unless repeatedly asked.  However, despite these weaknesses, this paper provides an intensive study of a serious of events providing conclusions as to cause and approaches for decreasing the risk of the occurrence of awareness.

            The authors presented eight suggestions based on their data that they feel will help reduce awareness (table 4 modified):  1) Check the anesthesia machine before each use; ensure a correctly mounted and filled vaporizer. 2) When using a volatile agent use an end-tidal agent monitor.  Use a low level alarm set for a sufficient volatile agent concentration to prevent awareness. 3)  Provide further hypnotic doses for repeated intubation attempts. 4) Be aware of the potential for awareness in hypovolemic patients receiving low concentrations of anesthetic.  Restore appropriate anesthetic concentration as soon as possible. 5) Routinely use a peripheral nerve stimulator and ensure sufficient anesthetic concentration until muscle power returns. 6) When using total intravenous anesthetics, ensure a patent intravenous line and periodically check the infusion pump to confirm drug administration. 7) Clearly label all drug syringes immediately when they are drawn up.  Check this label carefully before administration.  Do not rely on recognition of syringe size to confirm its contents.  Consider newer methods of ensuring that the correct drug is given. 8) Consider a depth of anesthesia monitor, if not routinely then for selected cases.

Bergman IJ et al: Awareness during general anesthesia: a review of 81 cases from the Anesthetic incident monitoring study (AIMS).  Anaesthesia 2002;57:549-556

David S. Smith, M.D., Ph.D.

Anesthesiologists and nurses apparantly infect patients with hepatitis C because of unsafe practices that have been previously demonstrated to transmit disease

It can be difficult to discern the exact nature of events from the initial news stories however it appears that physicians and nurses in an outpatient endoscopy clinic located in Las Vegas Nevada improperly drew doses of sedatives for patients from a single multi dose vial possibly exposing 40,000 patients to a risk of hepatitis C or aids.  Apparently they did not use a fresh syringe and needle for each entry into the vial so that transmission between patients via the vial contents was possible.  I cannot believe this has happened – it seems so contrary to every teaching on disease transmission and current safe practice.  Do not even consider reusing the same syringes or needles between patients.  Any item that is used on more than one patient should be designed for such use and properly disinfected between uses.

However the above is not a unique event.  On several occasions in the recent past anesthesiologists have been identified with transmitting Hepatitis C through the misguided practice of syringe/needle reuse and multi dose vials.  In 2002 there was a hepatitis C outbreak in Norman Oklahoma related to needle and syringe reuse.  About 71 people were infected there.  In 2007, an anesthesiologist from Dix Hills New York was associated with a cluster of Hepatitis C infections related to his practice.  As a result 11,000 of his former patients were contacted about infection risk.  Also in 2007 another anesthesiologist, was sued for Hepatitis C transmission from faulty infection control practice while giving anesthesia for colonoscopy.  This last anesthesiologist practiced at about 10 different physician offices and about 4,500 of his former patients were placed at risk because of his failure to use reasonable infection control.

The ASA newsletter (66:2002) provides a summary of the ASA infection control guidelines: 1) Syringes and needles are sterile, single-patient-use items. 2) After entry into or connection with a patient’s intravenous infusion, the syringe and needle should be considered contaminated and used only for that patient. 3) Medication from a syringe must not be administered to multiple patients even if the needle on the syringe is changed. 4) All infusion fluids, administration sets (intravenous tubing and connections) and pressure transducer setups are single-patient-use items. Absence of blood contamination cannot be guaranteed by visual inspection. 5) Sterile needles and syringes should always be used to aspirate the contents of an ampule or vial. 6) Each time a multidose vial is entered, aseptic techniques should be used, including cleansing the rubber stopper with alcohol and using a sterile needle and syringe. If visible contamination of a multidose vial has occurred or if sterility is questionable, the vial should be discarded. 7) Immediately after use, or at least at the end of each patient’s anesthetic, all used syringes and needles should be discarded in an appropriate puncture-resistant sharps container. Unused syringes, needles and related items should be stored in a clean area to avoid contamination by contaminated syringes and equipment. 8) Health care workers with breaks in the skin or exudative or weeping lesions should refrain from direct patient contact and from handling patient care equipment unless the open area can be protected. Strict attention to hand washing, hand antisepsis, aseptic technique and use of gloves and other barrier precautions is important to avoid transmission of pathogenic microorganisms to patients and health care workers.

There apparently persists the misguided concept that injecting high on the iv tubing is safe.  This is wrong!  The ASA Newsletter article cited above notes the following: In 1990, Trepanier et al. investigated the risk of cross-infection related to the multiple use of disposable syringes for anesthesia in the operating room. The rate of blood contamination in the intravenous (I.V.) tubing was 3.3 percent at the injection site closest to the I.V. catheter and 0.3 percent at the furthest site. The presence of a one-way check-valve did not affect the contamination rate. Trepanier and his group also found that changing the needle alone on a used syringe was useless for preventing contamination of blood into the syringe.

Considering the difficulty in maintaining sterility and preventing contamination of multi dose containers several states are considering a ban on their use for most medications.  Once a syringe is connected to a patient’s IV it is by definition contaminated and should never be used on another patient.  If a multidose vial has been entered by a syringe and needle that has been in contact with a patient that vial is also contaminated and should be discarded once the care of that patient is over.  It would be prudent not to use multidose vials between patients but to discard the remaining drug at the end of each case.  A Google news search on any of the key words mentioned will bring up the innumerable newspaper sources for this material.

Reference: Trepanier CA et al: Risk of cross-infection related to the multiple use of disposable syringes. Can J Anaesth 1990;37:156-159

David S. Smith, M.D., Ph.D.

Awareness - the ASA closed claim study - a detailed review

Some background information for those unfamiliar with the ASA closed claims project (this background information is taken from the closed claim website http://depts.washington.edu/asaccp/ASA/index.shtml ): Since 1985 the ASA has sponsored this project. At the time the project was initiated, professional liability insurance was expensive for anesthesiologists and in some states difficult to obtain. The intention of the Closed Claims Project was to identify causes of loss, improve patient safety, and thereby relieve the insurance problem for anesthesiologists.  The project consists of an in-depth investigation of 7328 closed insurance claims resulting from anesthetic mishaps. Data is gathered in the form of detailed case summaries collected by ASA member anesthesiologists from insurance company claim files. Claims for dental injury, a very common, well understood, and in most cases minor injury, are excluded. Claims in which the basic sequence of events and/or nature of the injury cannot be reconstructed from the information in the insurance files are also been excluded. This results in most cases being collected from mishaps resulting in lawsuits, as files in these cases contain the most extensive information. Cases are collected from throughout the United States on a continuous basis.  The database consists of standardized summaries of each case, including patient information (e.g. age, physical status), surgical procedure and positioning, anesthetic evaluation and technique, events leading to the injury or claim, type and severity of injury, outcome of litigation, and physician evaluations of potential for prevention and appropriateness of anesthesia care. The database also includes a brief narrative summary of each claim, describing the sequence of events and adding any pertinent information not contained in the standardized data collection form.

            In my opinion the closed claims project provides a unique resource of intensively studied case experiences in which there was an outcome that was not satisfactory to the patient or their family.  It does not allow the calculation of incidence as the denominator is not known.  Because of the length of time from law suit to settlement, the data in the closed claims project tends to be old.  Thus new areas of risk or trends in settlement costs are, in my opinion, difficult to determine from this data.

            The ASA closed claims analysis of awareness during anesthesia was published in 1999 and included claims for adverse outcomes that occurred between 1961 and 1995.  A total of 4183 claims were in the database.  Seventy nine claims were for awareness with a greater proportion occurring in the 1990s compared to earlier decades.  The proportion of claims in the database was similar to burns, aspiration pneumonia and myocardial infarction.  Compared to other claims awareness more often involved women, patients younger than 60 years of age, and elective surgery.  The severity of injury for awareness claims was lower than for the other claims.  Eighteen of the claims were for awake paralysis and 61 claims were for recall during general anesthesia. 

            Claims for awake paralysis were related to intravenous infusion errors or syringe swaps.  Succinylcholine drips accounted for 10 of the 18 claims (unlabelled, mislabeled, failure to check the label).  The period of risk was preinduction or during induction when a muscle relaxant was given instead of a sedative or hypnotic.

            The highest frequency of recall during general anesthesia was during the maintenance phase (49 of 61 claims).  Recollection included recollection of conversation, feeling surgery without pain, pain, paralysis, tracheal intubation, and severe panic.  Eighty four percent sustained temporary emotional distress; 10% developed posttraumatic stress disorders.  Recurrent nightmares were described in 16% of claims and psychotherapy was described in 13%.

            Factors associated with recall during general anesthesia included: nitrous – narcotic relaxant technique  without volatile anesthetic (11 of 61 claims), hypotension requiring discontinuation of the anesthetic agent (11 instances), inadequate dose of anesthetic for no obvious reason (8), difficult intubation (5), failure to adjust anesthetic dose for morbid obesity (8), vaporizer leak (5) and failure to turn on the vaporizer (3).  In 10 cases no obvious factor could be determined.  The classic cues for light anesthesia were absent in most cases.  Five factors were significantly associated with claims for recall compared to other general anesthesia claims: no volatile anesthetic agent, female gender, obstetric or gynecologic procedure, intraoperative opioid, and intraoperative muscle relaxant.  After adjusting for risk factors and application of multiple logistic analyses – female gender and anesthetic techniques using intra operative opioid and muscle relaxants without a volatile anesthetic increased the relative frequency of claims of recall.  OB/Gyn procedures were not an independent risk factor. (From Domino KB et al: Awareness during anesthesia: A closed claims analysis. Anesthesiology 1999;90:1053-1061.)

            DSS comments: The separation of “awake paralysis” from “recall” is not done in most subsequent studies.  Notice the frequency of a drug error with respect to the occurrence of awake paralysis.  Changes in practice (decreased use of succinylcholine infusions) may decrease this incidence.  However bags of non depolarizing muscle relaxants for infusion present the same potential risk unless clearly labeled and kept away from other intravenous solutions until the time of use.  Several of the instances of awake paralysis occurred because of a syringe swap or mislabeled syringe.  An argument might be made to keep syringes containing muscle relaxant separate from antibiotics, anxiolytics, narcotics and anesthesia induction drugs.  Finally using nitrous oxide without a volatile agent was associated with a large number of instances of recall.  Fortunately that practice has almost disappeared (at least at Hospital of the University of Pennsylvania).

David S. Smith, M.D., Ph.D.