Inadvertent intrathecal injections and best practice management.

The intrathecal space has become an important anatomic site for medical intervention not only in anesthesia practice, but also in many other medical specialties. Undesired/inadvertent intrathecal injections (UII) are generally rare. There is tremendous variation in reported inadvertent administrations via an intrathecal route in the literature, mainly as individual cases and very small case-series reports. This review aims to identify potential sources of UII, its clinical presentations, and appropriate management. The inadvertent injectants are classified as anesthetic agents and pain medicines, chemotherapeutics, radiological contrast agents, antibiotics and corticosteroids, and miscellaneous chemical agents such as tranexamic acid. The clinical effects of UII are dependent upon inadvertent injectant(s) and dose being administered intrathecally, and can range from no adverse effect to profound neurological consequences and/or death. Prompt cerebrospinal fluid (CSF) lavage and cardiopulmonary support seem to be the mainstay of treatment. If serious consequences are anticipated, CSF lavage could be lifesaving. This review additionally provides some options for comprehensive management and preventing strategies.

Hydrocodone bitartrate for chronic pain.

Hydrocodone bitartrate is the most commonly used drug for acute and chronic pain in the U.S. with over 135 million prescriptions in 2012. The U.S. is the primary consumer of hydrocodone, using 99% of the global supply for 4.4% of the global population. With its easy availability and abuse patterns, hydrocodone has been touted as a primary driver of opioid-related abuse and misuse. There are no clinical efficacy studies of hydrocodone in short-acting form in combination with acetaminophen or ibuprofen in chronic pain. Hydrocodone has been approved with two long-term formulations since 2014. The FDA has rescheduled hydrocodone from Schedule III to Schedule II which went into effect on October 6, 2014, along with a limit on added acetaminophen of 325 mg for each dose of hydrocodone. This review examines the evolution of hydrocodone into a common and yet controversial drug in the U.S. with its pharmacokinetics, pharmacodynamics, safety and efficacy.

Comparative study of three different supraglottic airway devices in simulated difficult airway situations.

BACKGROUND: Supraglottic airway devices (SAD) provide an effective way for managing difficult airways. Numerous SADs have been developed in recent years. We compared three SADs utilizing simulated airways. The major aim of this study was to provide evidence for the efficacy of SADs in the management of simulated difficult airway situations. METHODS: The study utilized an airway simulation manikin (Laerdal SimMan® 3G) to assess feasibility and time to final placement of three different airway devices (the classic laryngeal mask airway [LMA], the Laryngeal tube [LT], and the EasyTube® [EzT]). Thirty anesthesiologists inserted each of the SADs under standard physiologic airway conditions (STD) as well as pathological airway conditions, including tongue edema (TE) and trismus combined with limited mobility of the cervical spine (TCS), mimicking a patient with cramps. RESULTS: In STD and TE, all participants were able to successfully place the LMA, LT, and EzT correctly. In TCS, one participant failed to place the LMA correctly, whereas six participants failed to place the LT correctly (P=0.031). Under STD and TE conditions, we found a significantly longer time to final placement with the EzT (P=0.001). Under TCS conditions, there was no significant difference between the tested SADs. Under STD conditions, the participants rated the LMA best (P<0.001). Under TE and TCS condition, the EzT was significantly higher rated (P<0.001). CONCLUSION: The EzT showed benefits in two difficult airway situations (TE and TCS) in a prospective manikin study amongst anesthesiologists.

Morphine, opioids, and the feline pulmonary vascular bed.

BACKGROUND: Opioid-induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects. METHODS: This was a prospective vehicle-controlled study involving an intact chest preparation of adult mongrel cats. The effects of various opioids, morphine, fentanyl, remifentanil, sufentanil, and meperidine were compared with other vasodepressor agents. Additionally, the effects of L-N(5)-(1-iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide [selective cyclooxygenase (COX)-2 inhibitor], glibenclamide (ATP-sensitive K+ channel blocker), naloxone (non-selective opioid receptor antagonist), and diphenhydramine (histamine H(1)-receptor antagonist) were investigated on pulmonary arterial responses to morphine and other selected agonists in the feline pulmonary vascular bed. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. RESULTS: In the cat pulmonary vascular bed of the isolated left lower lobe, morphine, remifentanil, fentanyl, sufentanil, and meperidine induced a dose-dependent moderate vasodepressor response and it appeared that sufentanil was the most potent on a nanomolar basis. The effects of morphine were not significantly altered after administration of L-NIO, nimesulide, and glibenclamide. However, the vascular responses to morphine were significantly attenuated following administration of naloxone and diphenhydramine. CONCLUSION: The results of the present study suggest that sufentanil appears to have slightly more potency and morphine the least of the five opioid agonists studied on a nanomolar basis. Morphine-induced vasodilatory responses appeared to be mediated or modulated by both opioid receptor and histamine-receptor-sensitive pathways.

Peroxynitrite does not impair pulmonary and systemic vascular responses.

The effects of peroxynitrite (ONOO-) on vascular responses were investigated in the systemic and hindquarters vascular bed and in the isolated perfused rat lung. Intravenous injections of ONOO- decreased systemic arterial pressure, and injections of ONOO- into the hindquarters decreased perfusion pressure in a dose-related manner. Injections of ONOO- into the lung perfusion circuit increased pulmonary arterial perfusion pressure. Responses to ONOO- were rapid in onset, short in duration, and repeatable without exhibiting tachyphylaxis. Repeated injections of ONOO- did not alter systemic, hindquarters, or pulmonary responses to endothelium-dependent vasodilators or other vasoactive agonists and did not alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium nitrate or nitrite or decomposed ONOO- had little effect on vascular pressures. Pulmonary and hindquarters responses to ONOO- were not altered by a cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid. These results demonstrate that ONOO- has significant pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activity; that short-term repeated exposure does impair vascular responsiveness; and that responses to ONOO- are not dependent on cyclooxygenase product release.

Recovery of elderly patients from two or more hours of desflurane or sevoflurane anaesthesia.

BACKGROUND: The solubility of desflurane compared with sevoflurane suggests more rapid recovery from desflurane anaesthesia. This could be important after prolonged anaesthesia and fast recovery may be advantageous in the elderly where slow recovery of mental function is a concern. We compared emergence from desflurane vs sevoflurane in elderly patients undergoing two or more hours of anaesthesia. METHODS: Fifty ASA physical status I, II, or III patients, 65 yr of age or older, undergoing anaesthesia expected to last two or more hours were randomly assigned to receive desflurane/nitrous oxide or sevoflurane/nitrous oxide anaesthesia. Patients were given 1-2 microg x kg(-1) fentanyl i.v. and anaesthesia was induced with propofol 1.5-2.5 mg x kg(-1) i.v. and maintained with either desflurane 2-6% or sevoflurane 0.6-1.75% with nitrous oxide 65% in oxygen. Inspired anaesthetic concentrations were adjusted to obtain adequate surgical anaesthesia and to maintain mean arterial pressure within 20% of baseline values. Early and intermediate recovery times were recorded. Digit-Symbol Substitution Test (DSST) scores and Visual Analog Scale (VAS) scores for pain and nausea were recorded before pre-medication and every 15 min in the Post Anaesthesia Care Unit (PACU) until patients were discharged. RESULTS: Early recovery times are given as median, quartiles. The times to extubation (5 (4-9); 9 (5-13) min), eye opening (5 (3-5); 11 (8-16) min), squeezing fingers on command (7 (4-9); 12 (8-17) min); and orientation (7 (5-9); 16 (10-21) min) were significantly less (P<0.05) for desflurane than for sevoflurane. Intermediate recovery, as measured by the DSST and time to ready for discharge from the PACU (56 (35-81); 71 (61-81) min) was similar in the two groups. CONCLUSIONS: Early but not intermediate recovery times of elderly patients undergoing a wide range of surgical procedures requiring two or more hours of anaesthesia is significantly (P

Ephedrine in the cat lung vasculature.

BACKGROUND: Ephedrine is one of the most commonly used non-catecholamine sympathomimetic agents. It is used in operating rooms and critical care settings worldwide. While it has many side effects, its ability to rapidly raise blood pressure makes it an ideal agent to maintain homeostasis as well as in emergency situations. While its effects are known to be mediated by an alpha-mediated mechanism, the exact alpha subtype is unknown. In addition, no studies using ephedrine have been performed in the pulmonary vascular bed of the cat. METHODS: The effects of phentolamine, a non-selective alpha-receptor blocker, and prazosin, an alpha1-selective antagonist, were investigated on pulmonary arterial responses to ephedrine, phenylepherine, norepinephrine, and U-46619. Lobar arterial perfusion pressure was continuously monitored, electronically averaged, and recorded with constant flow in the isolated left lower lobe vascular bed of the cat. RESULTS: Phentolamine and prazosin significantly reduced vasoconstrictor pulmonary perfusion pressure increases induced by ephedrine. CONCLUSION: Ephedrine has significant vasopressor activity in the pulmonary vascular bed of the cat meditated predominantly by alpha1 adrenergic receptor activation.

Comparison of responses to novel nitric oxide donors in the feline pulmonary vascular bed.

Pulmonary vascular responses to the novel diazeniumdiolate nitric oxide (NO) donors diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt, were investigated and compared in the intact-chest cat. Under conditions of controlled blood flow, when tone in the pulmonary vascular bed had been raised to a high steady level, intralobar injections of diethylamine/NO (0.3-10 microg), diethylenetriamine/NO (10-30 microg), spermine/NO (10-30 microg), sulfite/NO (10-30 microg), and angeli's salt (10-30 microg) caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. In terms of relative vasodilator activity in the pulmonary vascular bed, the dose of the compounds that decreased lobar arterial pressure 4 mm Hg (ED(4) mm Hg) was significantly lower for diethylamine/NO compared to S-nitroso-N-acetylpenicillamine which was significantly less than diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt. The half-life of the vasodilator responses, as measured by 50% response recovery time, to diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt was similar for doses with similar magnitudes of vasodilation, while the half-life to S-nitroso-N-acetylpenicillamine was significantly less than the diazeniumdiolate NO donors. The present data demonstrate that the diazeniumdiolate NO donors diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt have potent but relatively short-lasting vasodilator activity in the pulmonary vascular bed of the cat.

Postoperative nausea and vomiting--a review.

Post operative nausea and vomiting (PONV) remains an unpleasant and persistent problem for patients undergoing surgery. In fact PONV are among the most important factors contributing to delay in discharge of patients and an increase in unanticipated admissions after ambulatory surgery. Anesthesia providers are most often blamed for PONV, sometimes rightfully so, many times wrongly so. PONV is a multifactorial issue involving many physiological and biological mechanisms. As the trend towards ambulatory surgery increases, PONV continues to pose serious challenges for anesthesia providers because the potential cost savings of performing surgeries on an ambulatory basis may be negated by unanticipated hospital admission. Although PONV may be unavoidable in some patients for reasons we do not fully understand, there are risk factors that can be identified. As anesthesiologists it is essential for us to understand the mechanisms involved in nausea and vomiting and the available perioperative treatment options. We must do whatever we can to prevent and treat PONV and improve patient outcome for both medical and economic reasons.

"Wiener klinische Wochenschrift": publication patterns 1990-2000.

The impact factor (Institute for Scientific Information, ISI, Philadelphia, PA, USA) is a widespread used and acknowledged source for judging the quality of a researcher. In addition the "Science Citation Index (SCI)" [Institute for Scientific Information (ISI)] provides the scientific community with a citations database indicating the number of cited references in indexed articles. For several reasons, the SCI seems to be more relevant. To evaluate the quality of the journal "Wiener klinische Wochenschrift", we assessed how often contributors to this journal have been cited during the last decade and which contributions have ranked as top papers. Moreover, with the aim of a more objective type of scientific evaluation, we have employed a new score, the "Citation Per Time Score (CPT-Score--the SCI divided by the number of years of observation, starting one year after publication). We have evaluated the total SCI for the years 1990 to 1994 and for the years 1995 to 1999. The number of total citations between the appearance of an article and the year 2000 was analyzed. The highest ranked publication of the whole decade (1990-2000) was a paper by G. Stanek with 40 citations. Furthermore, we have evaluated the "Top Ten Papers" of the journal. Interestingly, a steady increase of the total citation index of the journal "Wiener klinische Wochenschrift" over the last decade could be demonstrated. This study clearly shows that the citation rate of an article is not determined by the impact factor of the journal but rather the quality of the contribution. Moreover, the citation analysis of papers published in the last ten years in the "Wiener klinische Wochenschrift" shows a satisfactory citation rate for articles published in this journal. It is therefore definitely attractive to submit an article to a journal such as the "Wiener klinische Wochenschrift".

Effects of PKC isozyme inhibitors on constrictor responses in the feline pulmonary vascular bed.

The effects of Gö-6976, a Ca(2+)-dependent protein kinase C (PKC) isozyme inhibitor, and rottlerin, a PKC-delta isozyme/calmodulin (CaM)-dependent kinase III inhibitor, on responses to vasopressor agents were investigated in the feline pulmonary vascular bed. Injections of angiotensin II, norepinephrine (NE), serotonin, BAY K 8644, and U-46619 into the lobar arterial constant blood flow perfusion circuit caused increases in pressure. Gö-6976 reduced responses to angiotensin II; however, it did not alter responses to serotonin, NE, or U-46619, whereas Gö-6976 enhanced BAY K 8644 responses. Rottlerin reduced responses to angiotensin II and NE, did not alter responses to serotonin or U-46619, and enhanced responses to BAY K 8644. Immunohistochemistry of feline pulmonary arterial smooth muscle cells demonstrated localization of PKC-alpha and -delta isozymes in response to phorbol 12-myristate 13-acetate and angiotensin II. Localization of PKC-alpha and -delta isozymes decreased with administration of Gö-6976 and rottlerin, respectively. These data suggest that activation of Ca(2+)-dependent PKC isozymes and Ca(2+)-independent PKC-delta isozyme/CaM-dependent kinase III mediate angiotensin II responses. These data further suggest that Ca(2+)-independent PKC-delta isozyme/CaM-dependent kinase III mediate responses to NE. A rottlerin- or Gö-6976-sensitive mechanism is not involved in mediating responses to serotonin and U-46619, but these PKC isozyme inhibitors enhanced BAY K 8644 responses in the feline pulmonary vascular bed.

Effects of garlic extract (Allium sativum) on neutrophil migration at the cellular level.

Studies of the effects of garlic extract on oxidative and lipoprotein levels have yielded widely different findings. Leukocytes play an important role during many processes, including inflammation. They migrate from intravascular spaces into tissues and attack microorganisms. In a recent study, the inhibitory effects of the nonsteroidal antiinflammatory drug, ibuprofen, on leukocyte transmigration were demonstrated using an in vitro assay. Little is known about the cellular effects of garlic extracts (Allium sativum). The aim of the current study was to investigate the influence of garlic extract on leukocyte migration through endothelial cell monolayers and thereby evaluate a possible role in inflammatory processes. Human umbilical endothelial cells were cultured on microporous membranes to make an endothelial cell monolayer (ECM). Freshly isolated neutrophils were used in a recently described migration assay. The amount of untreated neutrophils migrating through the untreated ECM was used as control and set at 100%. Neutrophils and/or ECM were pretreated with garlic extract using moderate, higher, and lower concentrations. Moderate plasma concentrations of garlic extract inhibited neutrophil migration through ECM significantly (64 +/- 5.8% standard deviation [SD]; P < 0.05) when both cell types were treated, (a situation that may have clinical relevance). Treating either neutrophils or ECM alone showed significant reductions in migratory rate (neutrophils treated alone: 81 +/- 7.7% SD, P < 0.05; ECM alone: 70 +/- 6.7%, P < 0.05). Thus, garlic extract is identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. Treatment of both cell types has an additive effect. Endothelial cells seem to be more affected than neutrophils. Further investigations are necessary to understand the potential clinical consequences.

Perioperative considerations for the patient taking herbal medicines.

There has been a significant increase in the proliferation and use of dietary supplements known as neutraceuticals. Since 1994, herbal products have been regulated by the Dietary Supplement Health and Education Act (DSHEA), which does not require burden of proof to demonstrate premarketing safety and efficacy studies. Scientific literature and government policies have not adequately addressed this fast-emerging group of more than 20,000 health supplements. Lack of purity and standardization of these agents, combined with minimal education in traditional homeopathic medical education, has led to serious health-related problems including arrhythmias, cardiovascular compromise, strokes, and deaths. Even though 30% of our traditional medicines are derived from botanicals, most physicians are either unfamiliar or unwilling to develop any level of expertise with neutraceuticals. A review emphasizing perioperative considerations is provided of the history of herbal medicines, governmental policies, and specific herbal agent-drug interactions.

Perioperative considerations for the patient on herbal medicines.

Herbal medicines have enormous presence in the United States health care system. There is an increasing trend towards reimbursement of herbal medicines by insurance companies, which further encourage their utilization. Herbs are listed under the "supplement" category by the Food and Drug Administration. The Dietary Supplement and Health Education Act signed into law in October 1994, requires no proof of efficacy, no demonstration of safety, and sets no standards for quality control for the products labeled as "supplements" thereby increasing the risk of adverse effects of these herbs. The United States has experienced an epidemic of over-the-counter "natural" products over the last two decades; but there is little motivation for the manufactures to conduct randomized, placebo-controlled, double-blinded clinical trials to unequivocally prove the safety and efficacy of these drugs. Physicians, irrespective of their specialty, should not underestimate the potential risks associated with the use of herbs as reports indicate that within the last two decades, more than 100 herbogenic deaths have occurred, many serious complications have been reported, patients have required renal dialysis, renal transplantation and hepatic transplantation after taking botanicals. Internists must inquire about the patient's use of herbal products. In addition, the education of each patient regarding the serious, potential drug-herb interactions should be a routine component of preoperative assessment. The American Society of Anesthesiologists (ASA) recommends that all herbal medications should be discontinued 2-3 weeks prior to an elective surgical procedure. If the patient is not sure of the content of the herbal medicine, he/she should be urged to bring the container so that an attempt can be made to review the contents of the preparation. While such an action holds some promise in the elective setting, emergency care should be based on a thorough drug-intake history from the patient or a relative, if possible. Medical research and medical literature in general has not addressed this new group of health supplements, despite the fact that many of these herbs have the potential to cause serious health problems and drug interations. There is a need to conduct scientific clinical trials to study the anesthetic drug responses to commonly used neutraceutical agents.