Eric Willem Ackerman

Long-lasting Epidural Sensory Blockade by n-Butyl-p-Aminobenzoate in the Terminally Ill Intractable Cancer Pain Patient

An aqueous suspension of n-butyl-p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally in terminally ill cancer patients with intractable pain. The suspension consisted of 10% BAB and 0.025% of the nonionic surfactant polysorbate 80 in 0.9% sodium chloride. Twelve consecutive patients received epidural BAB because pain was uncontrollable either by palliative radiotherapy or oral or epidural administrations of analgesics. The catheter or injecting needle was positioned at the segmental level of the pain. Repeated epidural injections were administered. In all patients, long-lasting sensory blockade (segmental analgesia) occurred, accompanied by a marked reduction or even absence of pain. In all patients, treatment with epidural opioids, alone or combined with local anesthetics, was no longer necessary. Five of the 12 patients did not require further administration of oral opioids. Motor, bowel, and bladder function were well preserved. In 6 patients, extensive necropsy of the spinal cord and spinal nerves did not reveal pathomorphologic changes. The outer aspect of the dura showed signs of focal necrosis on microscopy, yet its collagen structure and thickness were unchanged. Epidurally, focal infiltrative reactions were seen. The epidural use of an extremely lipid-soluble--hence hydrophobic--local anesthetic, with an exceptionally low pKa (2.3), formulated in suspension of the base, is conceptually innovative and needs further investigation. The authors conclude that the epidural administration of a BAB suspension may be an effective alternative to the neurolytic agents alcohol and phenol and may replace procedures such as cordotomy. Further investigation to determine the safety of BAB in this patient group appears warranted.

Using a clinical decision support system to determine the quality of antimicrobial dosing in intensive care patients with renal insufficiency

Background The benefits on clinical practice of a clinical decision support system (CDSS) are predominantly determined by the quality of the clinical rules used in this system. Therefore, it is essential to investigate the performance and potential benefits on quality of care of these rules. Methods A clinical rule assisting physicians in selecting the appropriate dosage according to renal function of frequently prescribed antimicrobials was developed. In 2004, 1788 patients admitted to the intensive care unit (ICU) for more than 12 h were included in this retrospective study. The actual number of dosage adjustments without the support of the CDSS was compared with the theoretical number of dosage adjustments determined by the clinical rule in patients with moderate (creatinine clearance (Clcreat) 10–50 ml/min) and severe (Clcreat <10 ml/min) renal dysfunction. If dosage adjustment was omitted, the duration of excessive anti-infective dosing and extra drug costs involved was determined. Results Dosage adjustment of antimicrobials was omitted in 163 patients (86%) with moderate renal failure and 13 patients (54%) with severe renal failure. Excessive exposure was most frequently detected in patients receiving fluconazole and ciprofloxacin (median duration of 6 days). In our ICU alone, more than €16 000 (

Long-lasting Epidural Sensory Blockade by n-Butyl p-Aminobenzoate in the Dog: Neurotoxic or Local Anesthetic Effect?

19 000) can be saved annually by adjusting the dosage according to renal function of frequently prescribed antimicrobials. Conclusions Despite intensive monitoring of patients in the ICU, dosage adjustment of antimicrobials is often omitted. Implementing this clinical rule has the potential to contribute to a significant improvement in medication safety and is expected to generate substantial savings.

Physicians' responses to clinical decision support on an intensive care unit-Comparison of four different alerting methods

An aqueous suspension of n-butyl p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally and around ulnar nerves in dogs. The suspension consisted of 10% BAB and 0.025% polysorbate in 0.9% NaCl. Sensory effects were tested by electrical stimulation. Three epidural injections were given, and the dogs were killed after 21 days. The increase in stimulation threshold was comparable to the effect of lidocaine in a concentration between 0.5% and 1%. Increased sensory threshold lasted for days, whereas no long-lasting motor effects were observed. Pathomorphologic changes were found primarily in the dorsal spinal nerve roots, although slight changes were also found in the ventral spinal roots. White matter degeneration was found only in the lumbar dorsal columns. This result suggested Wallerian degeneration in the dorsal spinal nerves and was at variance with recently published data on epidural BAB. No changes were observed in the ulnar nerves. The authors demonstrated that the pathomorphologic changes were induced by the BAB suspension and not by the suspending additive polysorbate 80. It was postulated that the suspension of BAB, which contains particles of a median size of 15 microns, was mainly confined to the dorsal epidural space where neurolytic changes in axons of the dorsal spinal nerve roots and dorsal columns are induced. This may explain the long-lasting sensory effects seen in intractable cancer pain patients after epidural BAB administration. More research is necessary to define the distribution of BAB in nervous tissue after its epidural administration and to better characterize toxicity, neurolytic effects, and regeneration of nervous tissue after BAB administrations.

Strategy for development and pre-implementation validation of effective clinical decision support

BACKGROUND In intensive care environments, technology is omnipresent whereby ensuring constant monitoring and the administration of critical drugs to unstable patients. A clinical decision support system (CDSS), with its widespread possibilities, can be a valuable tool in supporting adequate patient care. However, it is still unclear how decision support alerts should be presented to physicians and other medical staff to ensure that they are used most effectively. OBJECTIVE To determine the effect of four different alert presentation methods on alert compliance after the implementation of an advanced CDSS on the intensive care unit (ICU) in our hospital. METHODS A randomized clinical trial was executed from August 2010 till December 2011, which included all patients admitted to the ICU of our hospital. The CDSS applied contained a set of thirteen locally developed clinical rules. The percentage of alert compliance was compared for four alert presentation methods: pharmacy intervention, physician alert list, electronic health record (EHR) section and pop-up alerts. Additionally, surveys were held to determine the method most preferred by users of the CDSS. RESULTS In the study period, the CDSS generated 902 unique alerts, primarily due to drug dosing during decreased renal function and potassium disturbances. Alert compliance was highest for recommendations offered in pop-up alerts (41%, n=68/166), followed by pharmacy intervention (33%, n=80/244), the physician alert list (20%, n=40/199) and the EHR section (19%, n=55/293). The method most preferred by clinicians was pharmacy intervention, and pop-up alerts were found suitable as well if applied correctly. The physician alert list and EHR section were not considered suitable for CDSSs in the process of this study. CONCLUSION The alert presentation method used for CDSSs is crucial for the compliance with alerts for the clinical rules and, consequently, for the efficacy of these systems. Active alerts such as pop-ups and pharmacy intervention were more effective than passive alerts, which do not automatically appear within the clinical workflow. In this pilot study, ICU clinicians also preferred pharmacy intervention and pop-up alerts. More research is required to expand these results to other departments and other hospitals, as well as to other types of CDSSs and different alert presentation methods.

Success factors and barriers for implementation of advanced clinical decision support systems

Objective Well-designed clinical decision support systems (CDSS) can reduce the problem of alert fatigue by generating patient-specific alerts. This paper describes a strategy for the development and pre-implementation validation of specific and relevant clinical rules in order to reduce alert fatigue. Methods A four-step development and validation strategy of clinical rules is presented. As an example, from March to September 2006 the ‘lithium therapy rule’ was developed with this strategy based on the Plan-Do-Check-Act cycle. 15 368 patients were retrospectively screened and 2503 patients were prospectively screened while the positive and negative predictive values (PPV/NPV) were continuously monitored. The first step is to confirm that the parameters used in the definitions are linked to the correct data in the electronic health record; the second step involves an expert team in the review process to assure that alerts generated are clinically relevant; in the third step the rule is adjusted to generate the right alerts in daily practice; and the fourth step ensures technical and therapeutic maintenance after implementation in practice. Results From September 2006 to July 2010 nine other rules were developed following exactly the same strategy. The 10 clinical rules developed showed a progression during the development and all resulted in a final therapeutic PPV of ≥89% before implementation, based on expert opinion. NPV was determined for five clinical rules and was always 100%. Conclusions The proposed strategy is effective for creating specific and reliable clinical rules that generate relevant recommendations. The inclusion of an expert team in the development process is an essential success factor. It is hoped that it will accelerate the widespread use of these promising decision support systems in practice.

Calculation of the Permeability Coefficient Should Take into Account the Fact That Most Drugs Are Weak Electrolytes

Ten years ago, the US Institute of Medicine (IOM) called for a massive redesign of the healthcare delivery system.(Committee on Quality of Health Care in America, 2001) Today it is clear that one of the goals, the nationwide use of an electronic medical record (EMR) by 2010, has failed to be reached as the process of adoption has been slow. Some may consider an EMR as a final destination, although in fact it is only the start point of a revolution in healthcare: the implementation of clinical decision support systems (CDSS) that ‘make it easy to do it right’.(James, 2001) These systems are able to address the large, potential additional value of the implementation of an EMR. When an EMR is available, this is already a step in the right direction, to have an easy and structured access to all patient data available for all healthcare professionals that need them. However, this is still a huge amount of data, but one should also have the ability to integrate all these data and use these data in making the right choices in therapy. Practice has shown that despite the availability of an EMR, still many medication errors are made. Therefore, CDSS are designed to aid clinical decision-making by matching patient characteristics to a computerized knowledge or rule base to generate patient-specific recommendations.(Kawamoto et al., 2005) In the trendsetting IOM reports ‘To Err is Human’ (2000) and ‘Crossing the quality chasm’ (2001), a CDSS was endorsed as one of the most powerful tools available for improving patient safety and healthcare quality.(Kohn et al., 2000;Committee on Quality of Health Care in America, 2001) It is difficult to accept that despite multiple opportunities and promising results, these systems instead of being common practice, still remain ‘next-generation’.(James, 2001) During the last five years, research gave more insight in the success factors that could accelerate the idle process of CDSS adoption. (Kawamoto et al., 2005; Garg et al., 2005;Nies et al., 2006) The conclusions however are not univocal because the reviews included a wide variety of systems ranging from computerised to non-computerised CDSS as well as from basic to advanced systems. Basic decision support includes checking on drug-drug interactions, duplicate therapy, drug-allergies and generalized drug dosing. Advanced CDSS, used in addition to basic CDSS, includes for example checking on contra-indications (disease and drugs), individualized dosing support during renal impairment or guidance

Aqueous suspension preparation for injection, method for producing the same and use thereof for producing pain relief

To the Editor:—Although I accept that the cleansing and sterilization of laryngoscope blades is a nuisance to nurses and other paramedical personnel, I do not think that the use of a condom to cover the laryngoscope blade is an answer to this problem. First, the condom cannot be assumed to be a barrier against the transmission of infection between cases. Damage to its integrity unnoticable by the naked eye can easily occur, particularly during contact with teeth or dental work in a difficult intubation. It is not an effective barrier and puts patients at risk of cross-contamination. Condoms are renowned for splitting when used for their intended purpose, and this is far more likely when used as described. Second, I also feel strongly that condom packets scattered around anesthetic rooms or empty packets in disposal bins will lead to anxiety among patients. Difficulty would also be encountered if patients inquire why an odd taste persists after anesthesia. I would certainly not like to be responsible for telling them not to worry—that is only the taste of the spermicidal jelly.