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

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.

MRI related injuries are increasing

The Joint Commission has just issued Sentinel Event Alert #38 on MRI accidents. http://www.jointcommission.org/SentinelEvents/SentinelEventAlert/sea_38.htm
            Based on the FDA’s accident reporting database (believed to represent significantly less than 10% of events), accidents in the MRI suite have experienced a dramatic increase. This increase is believed to reflect a number of combined risk factors including (1) greater attractive forces from newer magnet systems, (2) higher patient acuity levels, (3) increasing interventional applications and (4) growing numbers of sedation / anesthesia patients.
            The current Sentinel Event Alert identifies risks associated with several issues, including heating, implants that are contraindicated in the MR environment, and projectile / missile events.

Heating:
            Heating incidents can arise from improper positioning of the patient during the exam or incorrect settings on the MRI for a particular scan. Corrective actions can include providing insulation between the patient and the MRI, proper body positioning, and review of scan parameters.
Implants:
            A number of implants, both active devices such as pacemakers and passive implants such as aneurysm clips, can present significant dangers to patients when exposed to either static (unchanging) or time-varying magnetic fields. Other implants, such as the leads used in cardiac devices or nerve stimulators, can experience significant local heating as a product of the normal radiofrequency (RF) energies used during the MRI examination process. Corrective actions to prevent scanning of patients with contraindicated implants include a careful review of the patient’s medical record, patient interviews, education of referring physicians, and scrutiny of all identified surgical procedures. (For up-to-date information on the safety of implants, please visit http://www.MRIsafety.com or http://www.doctordoctor.biz )
Projectiles:
            Despite the near-universal awareness of MRI magnets’ extreme power of attraction, objects containing steel are regularly brought into MRI rooms where they are ‘sucked’ into the MRI scanner. Often, these objects are small enough to be removed by hand, but larger objects often require very expensive service calls to have them removed from the scanner. Small objects such as bobby pins and nail clippers, however, can – and do – cause injuries when drawn into MRI magnets, striking patients and/or staff. Corrective actions to prevent projectile accidents include increased vigilance in screening patients and objects, as well as the gowning of all patients. One specific recommendation of the Sentinel Event Alert is for the use of contemporary ferromagnetic detection (FMD) systems specifically designed to find projectile threats in the MRI suite. (For links to all three manufacturers of FMD systems, see http://www.MRI-Planning.com/vendor_links.html ) (from the NPSF patient safety foundation list server).

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.

Check lists in medical care

This article from The New Yorker magazine (December 10, 2007) discusses the role of check lists in dramatically reducing infection during a recent study of ICUs in Michigan. The article also discusses the benefits of check lists in other industries and wonders why “check lists” are not used more in medicine.  It reviews the concept that complex processes that create a high risk of bad outcome if steps in the process are missed will be completed more reliably when check lists are used to provide consistency and support human memory.  The tagline for the article is if something so simple can transform intensive care, what else can it do?

The link is http://www.newyorker.com/reporting/2007/12/10/071210fa_fact_gawande

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

Morphine and hydromorphone mix up

According to the Pennsylvania Patient Safety Authority (PSA, September 2007 Newsletter) morphine – hydromorphone mix ups outnumber all other medication pair errors.  A typical error involves using the same mg dose for hydromorphone as would be used for morphine.  One event occurred in a darkened operating room during laser surgery when prefilled syringes of morphine and hydromorphone were both available.  According to the PSA, “Mix-ups between morphine and hydromorphone are the most common and potentially serious errors that can occur involving two high-alert drugs.   This risk exists in almost every facility in Pennsylvania. Assume that this error will eventually happen in your facility.”  The PSA presents an 8 step approach to decreasing the probability of this error from occurring.  Among their suggestions are the following that I think are critical: Monitor patients. Implement policies that specify the scope, frequency, and duration of monitoring that should occur before discharging patients who have just received a parenteral narcotic. Educate staff. Provide safety information on the use of potent narcotics via newsletters and inservice meetings. Educate staff about the differences between hydromorphone and morphine, as some of the reported mix-ups have been due to the mistaken belief that hydromorphone is the generic name for morphine.  Educate patients. Prior to administration of a narcotic, repeat the name of the medication out loud to the patient as another source of confirmation. (http://www.psa.state.pa.us/psa/lib/psa/advisories/v4n3_september2007/sept_2007_v4_n3_article_mixup_morphine_hydromorphone.pdf ).

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

what are the known causes of awareness during general anesthesia?

Bergman et al (1) examined 81 cases from the Australian voluntary, anonymous reporting data base in which awareness during surgery was reported.  The found that 50 cases were definitely aware and 31 cases had a high probability of awareness.  In 13 of the cases the patients appeared to have received an adequate anesthetic.  Where cause could be determined, in 32 cases there was an error in drug handling that resulted in paralysis of an awake patient and in 16 cases there was failure to deliver volatile anesthetic.  Other causes included prolonged attempts at tracheal intubation (5 cases) and deliberate withdrawal of the volatile anesthetic due to hemodynamic instability (4 cases).

Reference:  1) Bergman IJ et al: Awareness during general anesthesia: a review of 81 cases from the anaesthesia incident monitoring study. Anaesthesia 2002;57:549-556

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

Consequences of Beach Chair shoulder surgery

When concepts of and monitoring techniques to help maintain cerebral perfusion are not appreciated there may be significant consequences for patients.  Cullen & Kirby described patients undergoing shoulder surgery in the Beach Chair position who suffered massive brain injury.  Though the exact causes may never be determined, Cullen & Kirby believe that in the cases they reviewed the blood pressure was inadequate to maintain cerebral perfusion (see APSF Newsletter 2007;22:25-27 and Pohl A & Cullen DJ: Cerebral ischemia during shoulder surgery in the upright position: a case series. J Clin Anesth 2004;17:463-469).  The safe principles for providing anesthesia in the sitting position have been worked out by generations of neuroanesthesiologists who have cared for patients in this position since the early 1900s.  Issues related to the fall in blood pressure at brain level compared to heart level when the patient is sitting, air emboli, sciatic neuropathy from excessive hip flexion, brachial plexopathy from shoulder sag, anterior spinal artery syndrome from excess neck flexion, lingual swelling from an oral airway combined with neck flexion, and buttock ulceration from the body weight being borne by the ischial tuberosities are well known as are the techniques that help minimize these risks (Smith DS & Osborne I: Posterior Fossa: Anesthetic considerations in Cottrell JE & Smith DS (eds): Anesthesia and Neurosurgery, 4^th edition, 2001 pages 335 – 351).

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

Rapid response teams reduce mortality

Dacey and associates studied the incidence of cardiac arrests that occurred outside the intensive care unit starting 5 months before and ending 13 months after the introduction of a rapid response team (RRT) led by physician assistants with specialized critical care training.  Prior to the RRT there was an average of 7.6 cardiac arrests per 1000 discharges per month.  After the introduction of the RRT the number of cardiac arrests decreased to 3.0 per 1000 discharges per month.  There were a total of 344 RRT calls during the 13 month post introduction study period.  The percentage of unplanned ICU admissions decreased from 45% to 29% pre and post RRT (The effect of a rapid response team on major clinical outcome measures in a community hospital.  Crit Care Med 2007;35:2076 – 2082).

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