Diagnostic heuristics in dermatology, part 2: metacognition and other fixes.

Diagnostic errors are the most common, costly and dangerous of medical mistakes. In part 1 of this series, we described how general and dermatology-specific cognitive and perceptual biases underlie most of our correct diagnoses, as well as being a source of diagnostic medical errors. In this second part of the series, we describe some tactics to combat diagnostic error. Metacognition, or thinking about how we think, is the central approach advocated to avoid errors of 'uncritical' diagnostic thinking. Current individual and medical cultural attitudes need to be modified in order to incorporate improvements in diagnosis. Algorithms, artificial intelligence and system changes are being developed to address error and improve diagnostic accuracy.

Cognitive and visual diagnostic errors in dermatology: part 1.

Sir William Osler famously, and ironically, stated that 'Medicine is a science of uncertainty and an art of probability'. The processes by which each physician metes out diagnostic uncertainty and navigates probabilities in dermatology is far from uniform. While certain ubiquitous cognitive and visual heuristics can enhance diagnostic speed, they also create pitfalls and thinking traps that introduce significant variation in the diagnostic process. Discussed in this part of a two-part article are various cognitive and visual heuristics as they pertain to skin disease, with an introduction and special attention paid to the heuristic methods classically applied by dermatologists. How to best address error and improve our thought processes will be addressed in part 2.

Cutaneous manifestations of endocrine neoplasia.

Skin serves as a window to the wellbeing and disease in a person. The recognition of cutaneous markers of endocrine neoplasia can allow for the early diagnosis of tumors, for early treatment and ultimately prevention of morbidity and mortality secondary to malignancy. The following review outlines the various endocrine neoplasias which can present with cutaneous manifestations. The pathogenesis and general manifestations are reviewed as well as the cutaneous manifestations of the endocrine neoplasia. Diagnosis and management are discussed. A summary of the familial endocrine neoplastic syndromes, including the six Multiple Endocrine Neoplasia Syndromes are reviewed. A current understanding of this subject will allow for better diagnosis and recognition of endocrine tumors as they present with skin signs and symptoms.

The effect of heparin-coated pulmonary artery catheters on activated coagulation time in cardiac surgical patients.

OBJECTIVE: To investigate the effect of heparin-coated pulmonary artery catheters (HPACs) on activated coagulation time (ACT) drawn through a non-heparin-coated introducer sheath. DESIGN: A prospective, observational study. SETTING: University teaching hospital. PARTICIPANTS: Patients scheduled for surgical procedures requiring cardiopulmonary bypass. INTERVENTIONS: With institutional review board approval, 63 patients without prior coagulopathy undergoing procedures requiring cardiopulmonary bypass were studied. Jugular venous and radial arterial ACTs were measured before and immediately after insertion of an HPAC. Additional measurements were obtained 1 hour later and 4 minutes after completion of protamine infusion. MEASUREMENTS AND MAIN RESULTS: The ACT drawn from the introducer after placement of an HPAC was 48 seconds greater than the ACT drawn before the HPAC was placed (p < 0.0001). This difference was still present 1 hour later but not after the administration of protamine or in blood drawn at any time from another site. Baseline ACTs drawn from radial arterial catheters, kept patent using a heparin flush system, resulted in elevated measurements, despite withdrawing seven times the deadspace before taking a sample. CONCLUSIONS: Blood obtained from an introducer with an HPAC in situ provides a spuriously high ACT. ACTs drawn from catheters kept patent using heparin flush also result in prolonged measurements. Baseline ACT measurement from an introducer should be obtained before placement of the HPAC.

Incorporating palliative care into critical care education: principles, challenges, and opportunities.

OBJECTIVE: To identify the goals and methods for medical education about end-of-life care in the intensive care unit (ICU). DATA SOURCES AND STUDY SELECTION: A status report on palliative care, a summary report of recent research on palliative care education, articles in the medical literature on end-of-life care and critical care, and expert opinion were considered. DATA EXTRACTION: A working group, including specialists in critical care, palliative care, medical ethics, consumer advocacy, and communications, was convened at the "Medical Education for Care Near the End of Life National Consensus Conference." A modified nominal group process was used to develop a consensus. DATA SYNTHESIS: In the ICU, life and death decisions are often made in a crisis mode or in the face of uncertainty, and may necessitate the withholding and withdrawal of life-supporting technologies. Because critical illness often diminishes the capacity of patients to make decisions, clinicians must often make decisions in conjunction with surrogates, rather than with patients. Discontinuity of care can threaten trusting relationships, and cultural diversity can have a particularly powerful impact on choices for care. In the face of these realities, it is possible and appropriate to give compassionate palliative care to dying patients and their families in the ICU. CONCLUSIONS: Teaching care of the dying in the ICU should emphasize the following: a) the goals of care should guide the use of technology; b) understanding of prognostication and treatment withholding and withdrawal is essential; c) effective communication and trusting relationships are crucial to good care; d) cultural differences should be acknowledged and respected; and e) the delivery of excellent palliative care is appropriate and necessary when patients die in the ICU.

Effect of sevoflurane and desflurane on the myogenic constriction and flow-induced dilation in rat coronary arterioles.

BACKGROUND: Determinants of myocardial blood flow distribution include metabolic, myogenic, endothelial, and neurohumoral control mechanisms. The authors studied the effect of sevoflurane and desflurane on the myogenic and endothelial mechanisms. METHODS: Wistar rat subepicardial microvessels, approximately 100 microm in diameter, were monitored for diameter changes in vitro using a video detection system. Myogenic vasomotion was studied by varying the intraluminal pressure from 10 mmHg to 120 mmHg. Flow-induced, endothelium-dependent dilation was evaluated in U46619-preconstricted vessels by varying the pressure gradient across the isolated vessel from 10 mmHg to 80 mmHg, while maintaining the midpoint luminal pressure constant at 40 mmHg to avoid myogenic effects. Myogenic and flow-induced vasomotion both were studied in the presence of sevoflurane, 1 or 2 minimum alveolar concentration (MAC) (MAC is a unit of inhalational anesthetic potency), desflurane, 1 or 2 MAC, or no anesthetic (control). RESULTS: Myogenic constriction was shown above intraluminal pressures of 70 mmHg. Myogenic constriction was unchanged by sevoflurane, 1 MAC (P = 0.24), but was mildly enhanced by sevoflurane, 2 MAC (P < 0.05), or desflurane, 1 (P < 0.05) or 2 MAC (P < 0.01). Flow-induced dilation was shown over the pressure gradient range of 10-80 mmHg. Flow-induced dilation was not altered significantly by sevoflurane, 1 or 2 MAC (P > 0.3 each), but was significantly attenuated by desflurane, 1 or 2 MAC (P < 0.001 each). CONCLUSIONS: Sevoflurane maintains myogenic and endothelial determinants of myocardial blood flow distribution. Conversely, desflurane attenuates endothelium-dependent flow-induced dilation while mildly enhancing myogenic constriction.

Flow-induced dilation of rat coronary microvessels is attenuated by isoflurane but enhanced by halothane.

BACKGROUND: Volatile anesthetics attenuate agonist-induced endothelium-dependent vasodilation of coronary arteries. This study considered the hypothesis that the anesthetics may also attenuate flow-induced endothelium-dependent vasodilation. METHODS: Rat subepicardial arteries of approximately 100 microm were monitored for diameter changes in vitro by a video detection system, with the midpoint luminal pressure held constant at 40 mmHg but the pressure gradient (and therefore flow) across each vessel increased from 0 to 80 mmHg, in the presence or absence of 1 or 2 minimum alveolar concentration (MAC) isoflurane or 1 or 2 MAC halothane, with or without 10 microM of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) or 10 microM of the cyclooxygenase inhibitor indomethacin. RESULTS: Flow-induced dilation was attenuated by L-NNA or indomethacin (p < 0.001 each). It was attenuated by isoflurane in a concentration-dependent manner (P < 0.001). Attenuation by 2 MAC isoflurane persisted even in the presence of L-NNA (P < 0.01) or indomethacin (P < 0.05). On the other hand, flow-induced dilation was enhanced by 2 MAC halothane (P < 0.05). Halothane at 1 MAC had no significant effect. Enhancement by 2 MAC halothane was evident in the presence of indomethacin (P < 0.05) but not L-NNA (P = 0.40). CONCLUSIONS: In rat subepicardial arteries, flow-induced dilation is endothelium-dependent and mediated by both NO and a prostanoid. Isoflurane attenuates flow-induced dilation, possibly by decreasing synthesis, the action of NO and a prostanoid, or both, whereas halothane enhances it, possibly by increasing synthesis, the action of NO, or both.

Epithelial dependence of the bronchodilatory effect of sevoflurane and desflurane in rat distal bronchi.

UNLABELLED: The bronchial epithelium releases substances that enhance bronchodilation in response to certain bronchodilators. We examined the hypothesis that the bronchodilatory effect of desflurane and sevoflurane depends on the epithelium in rat distal bronchial segments. Wistar rat subsegmental bronchial segments (diameter approximately 100 microm) were dissected. After preconstriction with 5-hydroxytryptamine, each segment was exposed to increasing concentrations of desflurane 0%-12% or sevoflurane 0%-4.8% under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NNA), after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. Both desflurane and sevoflurane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 54% +/- 8% [mean +/- SD] dilation for 12% desflurane and 48% +/- 14% dilation for 4.8% sevoflurane). For both anesthetics, bronchodilation was significantly attenuated by epithelial rubbing (15% +/- 4% dilation for 12% desflurane and 13% +/- 10% dilation for 4.8% sevoflurane; P < 0.001 each), by pretreatment with indomethacin (12% +/- 3% dilation for 12% desflurane and 9% +/- 5% dilation for 4.8% sevoflurane; P < 0.001 each), and by L-NNA (24% +/- 8% dilation for 12% desflurane, P < 0.001; and 17% +/- 10% dilation for 4.8% sevoflurane, P < 0.01). Desflurane- and sevoflurane-mediated bronchodilation depends at least partially on the epithelium, and may involve both a prostanoid and NO in rat distal bronchi. IMPLICATIONS: Bronchodilation by the volatile anesthetics desflurane and sevoflurane is at least partially epithelium-dependent and may be attenuated in diseases affecting the epithelium, such as asthma.

Effect of isoflurane on the beta-adrenergic and endothelium-dependent relaxation of pig cerebral microvessels after cardiopulmonary bypass.

We examined the direct vasomotor effect of isoflurane as well as its effect on endothelium-dependent and beta-adrenergic vasodilation of cerebral microcirculation following either normothermic cardiopulmonary bypass (CPB) or profoundly hypothermic CPB with circulatory arrest. Pigs were placed on CPB; the systemic temperature was either maintained at 37 degrees C or lowered to 15 degrees C with 60 minutes of circulatory arrest. After 2 hours of CPB, the animals were separated from CPB; 15 minutes later the brain was quickly harvested in cold Krebs solution. Control animals were not instrumented and their brains were similarly harvested. Arteries of approximately 100 microm were dissected and changes in diameter monitored by in vitro videomicroscopy. Following preconstriction with the thromboxane analogue U46619 1 micromol/L, percent relaxation to the endothelium-dependent dilator adenosine diphosphate (ADP) 10(-9) to 10(-4) mol/L, the endothelium-independent dilator sodium nitroprusside (SNP) 10(-9) to 10(-4) mol/L, or the beta-adrenergic agonist isoproterenol 10(-12) to 10(-4) mol/L was measured either in the presence or absence of isoflurane 2%. Additionally, with or without preconstriction with U46619 1 micromol/L, vessel diameter changes were monitored with increasing concentrations of isoflurane 0-3%. Dose-response curves were compared by two-way analysis of variance. Vasodilation to ADP or isoproterenol, but not SNP, was attenuated after normothermic CPB (N-CPB) or profoundly hypothermic CPB (PH-CPB). Although isoflurane attenuated vasodilation of control vessels to ADP or isoproterenol, isoflurane did not further attenuate vasodilation to ADP or isoproterenol after N-CPB or PH-CPB. The direct vasomotor effect of isoflurane depended on the preexisting tone of the vessels, constricting vessels without preconstriction and dilating them after preconstriction. These findings may have implications on the incidence of neuropsychological dysfunction after CPB and use of isoflurane.

The direct vasomotor effect of thyroid hormones on rat skeletal muscle resistance arteries.

UNLABELLED: The present study examines the hypothesis that the hormones have direct vasodilatory effects and attempts to determine whether the effects are endothelium-dependent. Rat skeletal muscle resistance arteries of approximately 100 microns were dissected, and vessel diameter changes were monitored using a videodetection system. After equilibration at 37 degrees C, each vessel was preconstricted with the thromboxane analog U46619 1 microM, and the percentage of dilation was measured after exposure to increasing concentrations of triiodothyronine (T3) or levothyroxine (T4) (10(-10) to 10(-7) M). Dilation in response to T3 was also measured after endothelial denudation and pretreatment with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) 10 microM, the cyclooxygenase inhibitor indomethacin 10 microM, the adenosine triphosphate-sensitive K+ channel blocker glibenclamide 1 microM, or the beta-adrenergic antagonist propranolol 1 microM. Both T3 and T4 demonstrated concentration-dependent dilation of the U46619-preconstricted vessels (P < 0.001 each), with T3 having a greater effect than T4 (P < 0.05) (36% +/- 9% [mean +/- SD] dilation at 10(-7) M T3 vs 24% +/- 6% dilation at 10(-7) M T4). In comparison, isoproterenol 10(-7) M produced 56% +/- 6% dilation. T3-mediated vasodilation was attenuated but not abolished by endothelial denudation (18% +/- 3% dilation at 10(-7) M T3) (P < 0.01), L-NNA (15% +/- 7% dilation at 10(-7) M T3) (P < 0.01), indomethacin (20% +/- 9% dilation at 10(-7) M T3) (P < 0.05), and glibenclamide (22% +/- 7% dilation at 10(-7) M T3) (P < 0.01), but it was not affected by propranolol (37% +/- 20% dilation at 10(-7) M T3) (P = 0.99). We conclude that thyroid hormones possess direct vasodilatory effects with both endothelium-independent and endothelium-dependent components. IMPLICATIONS: Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroidism or when administered pharmacologically in cardiac surgery.

Isoflurane- and halothane-mediated dilation of distal bronchi in the rat depends on the epithelium.

BACKGROUND: Respiratory epithelium releases substance(s) that can modulate bronchoconstriction in response to constrictive agonists and enhance bronchodilation in response to certain bronchodilators. The hypothesis that the bronchodilatory effect of isoflurane and halothane depends on the epithelium was tested in rat distal bronchial segments. METHODS: Wistar rat bronchial segments of the fourth order (diameter approximately 100 microns) were dissected. After preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine, after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. RESULTS: Both isoflurane and halothane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD] dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both anesthetics, bronchodilation was significantly but incompletely attenuated by epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/- 10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20% +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3% halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P < 0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing did not impair nitroprusside-associated bronchodilation. CONCLUSIONS: Isoflurane- and halothane-mediated bronchodilation depends at least partially on the epithelium and may involve both a prostanoid and nitric oxide in distal rat bronchi.