Global obstetric anaesthesia: bridging the gap in maternal health care inequities through partnership in education.

Maternal mortality rates are unacceptably high globally. Low- and middle-income countries (LMICs) face challenges of an inadequate anaesthesia workforce, under-resourced healthcare systems and sub-optimal access to labour and delivery care, all of which negatively impact maternal and neonatal outcomes. In order to effect the changes in surgical-obstetric-anaesthesia workforce numbers advocated by the Lancet Commission on Global Surgery to support the UN sustainable development goals, mass training and upskilling of both physician and non-physician anaesthetists is imperative. The implementation of outreach programmes and partnerships across organisations and countries has already been shown to improve the provision of safe care to mothers and their babies, and these efforts should be continued. Short subspecialty courses and simulation training are two cornerstones of modern obstetric anaesthesia training in poorly resourced environments. This review discusses the challenges to accessing quality maternal healthcare in LMICs and the use of education, outreach, partnership and research to protect the most vulnerable women from coming to harm in the peripartum period.

Why are women still dying from obstetric hemorrhage? A narrative review of perspectives from high and low resource settings.

The possibility of hemorrhage will always co-exist with pregnancy, whether anticipated or not. It remains the unwelcome guest in the corner of every delivery room, stealing the lives of young women every day across the globe. In 2014, the World Health Organization reported that hemorrhage was the leading contributor to maternal mortality worldwide, with nearly 75% of maternal deaths due to postpartum hemorrhage. In low resource settings, while maternal mortality is decreasing, hemorrhage remains the single most important contributor to maternal death. Hospital-based deliveries with skilled birth attendants have been encouraged to improve outcomes and, as a result, hospital births have dramatically increased. However, access to higher levels of emergency obstetric care as well as blood products and therapeutic resources remain limiting factors. Meanwhile, in high resource settings, maternal mortality from hemorrhage is increasing, particularly among women of color. While very rare, mortality from hemorrhage generally follows medical interventions such as surgical management of placenta accreta or emergency cesarean section. Primary prevention therefore requires careful selection and conduct of medical interventions, as well as the provision of high quality, supportive, and safe maternity care. It is clear that there is not one single solution in preventing obstetric hemorrhage on a global scale. The international community must employ creative solutions to reduce this ever-present problem.

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid.

Establishing an obstetric neuraxial service in low-resource areas.

The proportion of laboring women utilizing neuraxial techniques for labor analgesia has steadily increased over the past decades in North America, the UK and parts of Europe. Anesthesiologists in many other countries may want to introduce an obstetric neuraxial service but may lack the knowledge and experience necessary to ensure its safety. The focus of this article is to address the necessity, benefit and challenges of establishing such a service in a resource-limited environment. Even successful financial institutions may be considered resource-limited if critical components necessary for an obstetric neuraxial service are missing due to either perceived unimportance or non-availability. There is a need to deploy a culture of safety by ensuring the availability of resuscitation equipment, developing protocols and training, fostering communication among members of the care team and initiating quality-control measures. Patient education and satisfaction are additional key components of a successful service. Even in financially low-resource settings, proper safety measures must be adopted so that the neuraxial procedure itself does not contribute to morbidity and mortality. A viable and safe neuraxial service can be developed using innovative strategies based on local constraints.

Ultraviolet radiation and the risks of cutaneous malignant melanoma and non-melanoma skin cancer: perceptions and behaviours of Danish and American adolescents.

The highest prevalence rates of skin malignancy in the northern hemisphere occur in Scandinavia and the United States (USA). Most Danes and Americans receive 50% of their lifetime ultraviolet (UV) radiation before the age of 21, making it important to address sun exposure risks with adolescents. The project was undertaken to determine differences between Danish and American adolescents in knowledge of sun exposure and skin malignancy, activities accounting for sun exposure, and means used for sun protection. Questionnaires regarding skin cancer and sun exposure were distributed to 674 secondary school age students in Hilleroed, Denmark, and to 483 similarly aged students in Winston-Salem, North Carolina, USA. Differences in responses between and within groups were compared. American adolescents had more knowledge of the characteristics and malignant potential of melanoma than did Danish adolescents. Danish youth and females from both countries were significantly more likely to engage in sunbathing and tanning bed use. Black Danish students reported significantly more sunburn and were more likely to sunbathe or use a tanning bed than were black American students. Danish students were more likely than Americans to use sunscreen, however, Americans were more likely to apply sun protective factor (SPF) 15 or greater. In conclusion, given that sunbathing and tanning bed use are associated with the development of precancerous lesions and skin malignancy, Danish teens are at increased risk. The rates of skin malignancy are relatively high in Scandinavia and efforts to improve understanding of exposure and cancer risks should be undertaken in adolescents.

Inheritance of evolved glyphosate resistance in Conyza canadensis (L.) Cronq.

N-(phosphonomethyl)glycine (glyphosate) resistance was previously reported in a horseweed [Conyza (=Erigeron) canadensis (L.) Cronq.] population from Houston, DE (P (0) (R) ). Recurrent selection was performed on P (0) (R) , since the population was composed of susceptible (5%) and resistant (95%) phenotypes. After two cycles of selection at 2.0 kg ae glyphosate ha(-1), similar glyphosate rates that reduced plant growth by 50%, glyphosate rates that inflicted 50% mortality in the population, and accumulations of half of the maximum detectable shikimic acid concentration were observed between the parental P (0) (R) and the first (RS(1)) and second (RS(2)) recurrent generations. In addition, RS(1) and RS(2) did not segregate for resistance to glyphosate. This suggested that the RS(2) population comprised a near-homozygous, glyphosate-resistant line. Whole-plant rate responses estimated a fourfold resistance increase to glyphosate between RS(2) and either a pristine Ames, IA (P (0) (P) ) or a susceptible C. canadensis population from Georgetown, DE (P (0) (S) ). The genetics of glyphosate resistance in C. canadensis was investigated by performing reciprocal crosses between RS(2) and either the P (0) (P) or P (0) (S) populations. Evaluations of the first (F(1)) and second (F(2)) filial generations suggested that glyphosate resistance was governed by an incompletely dominant, single-locus gene (R allele) located in the nuclear genome. The proposed genetic model was confirmed by back-crosses of the F(1) to plants that arose from achenes of the original RS(2), P (0) (P) , or P (0) (S) parents. The autogamous nature of C. canadensis, the simple inheritance model of glyphosate resistance, and the fact that heterozygous genotypes (F(1)) survived glyphosate rates well above those recommended by the manufacturer, predicted a rapid increase in frequency of the R allele under continuous glyphosate selection. The impact of genetics on C. canadensis resistance management is discussed.

Incidence and characteristics of failures in obstetric neuraxial analgesia and anesthesia: a retrospective analysis of 19,259 deliveries.

A retrospective analysis was performed on 19,259 deliveries that occurred in our institution from January 2000 to December 2002. Anesthesia records and quality assurance data sheets were reviewed for the characteristics and failure rates of neuraxial blocks performed for labor analgesia and anesthesia. The neuraxial labor analgesia rate was 75% and the overall failure rate was 12%. After adequate analgesia from initial placement, 6.8% of patients had subsequent inadequate analgesia during labor that required epidural catheter replacement. Ultimately 98.8% of all patients received adequate analgesia even though 1.5% of patients had multiple replacements. Six percent of epidural catheters had initial intravenous placement but 46% were made functional by simple manipulations without higher subsequent failure. Unintended dural puncture occurred in 1.2% of labor neuraxial analgesia. The incidences of overall failure, intravenous epidural catheter, wet tap, inadequate epidural analgesia and catheter replacement were lower in patients receiving combined spinal-epidural versus epidural analgesia. For cesarean section, 7.1% of pre-existing labor epidural catheters failed and 4.3% of patients required conversion to general anesthesia. Spinal anesthesia for cesarean section had a lower failure rate of 2.7%, with 1.2% of the patients requiring general anesthesia. The overall use of general anesthesia decreased from 8% to 4.3% over the three-year period. Furthermore, regional anesthesia was used in 93.5% of cesarean deliveries with no anesthetic-related mortalities. Future investigations should identify acceptable international standards, risk factors associated with failure and methods to reduce failure before cesarean section.

Effects of weed management systems on canopy insects in herbicide-resistant soybeans.

The effects of transgenic herbicide-resistant soybean varieties and their corresponding weed management strategies on canopy insects were examined in studies at two locations in Iowa in 1997 and 1998. Weed management systems that allowed more weed escapes typically had higher insect population densities. However, systems with fewer weeds seemingly were preferred by potato leafhoppers. Bean leaf beetles and potato leafhoppers showed preferences for certain soybean varieties, but these effects were attributed to soybean plant height. These findings indicate that although the transgenic soybean varieties did not strongly affect insect populations, weed management systems can affect insect populations in soybean. However, this impact is likely related more to weed suppression effectiveness than to a direct effect of the herbicides on the insects.

Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine.

Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide that is synthesized through the posttranslational processing of beta-endorphin in brain stem regions that control respiration and autonomic function. This study tested the hypothesis that Gly-Gln administration to conscious rats will prevent the respiratory depression caused by morphine without affecting morphine antinociception. Rats were administered Gly-Gln (1-100 nmol) or saline (10 microl) intracerebroventricularly followed, 5 min later, by morphine (40 nmol icv). Arterial blood gases and pH were measured immediately before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatment inhibited morphine-induced hypercapnia, hypoxia, and acidosis significantly. The response was dose dependent and significant at Gly-Gln doses as low as 1 nmol. In contrast, Gly-Gln (1-300 nmol) had no effect on morphine-evoked antinociception in the paw withdrawal test. When given alone to otherwise untreated animals, Gly-Gln did not affect nociceptive latencies or blood gas values. These data indicate that Gly-Gln inhibits morphine-induced respiratory depression without compromising morphine antinociception.

Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia.

BACKGROUND: Intrathecal (IT) opioid and local anesthetic combinations are popular for labor analgesia because of rapid, effective pain relief, but the duration of analgesia is limited. This study was undertaken to determine whether the addition of clonidine and neostigmine to IT bupivacaine-fentanyl would increase the duration of analgesia without increasing side effects for patients in labor. METHODS: Forty-five healthy parturients in active labor were randomized to receive a 2-ml IT dose of one of the following dextrose-containing solutions using the combined spinal-epidural technique: (1) bupivacaine 2.5 mg and fentanyl 25 microg (BF); (2) BF plus clonidine 30 microg (BFC); or (3) BFC plus neostigmine 10 microg (BFCN). Pain, sensory levels, motor block, side effects, maternal vital signs, and fetal heart rate were systematically assessed. RESULTS: Patients administered BFCN had significantly longer analgesia (165+/-32 min) than those who received BF (90+/-21 min; P<0.001) or BFC (123+/-21 min; P<0.001). Pain scores, block characteristics, maternal vital signs, Apgar scores, maternal satisfaction, and side effects were similar among groups except for nausea, which was significantly greater in the BFCN group (P<0.05 as compared with BFC). CONCLUSIONS: The addition of clonidine and neostigmine significantly increased the duration of analgesia from IT bupivacaine-fentanyl during labor, but neostigmine caused more nausea. Although serious side effects were not observed in this study, safety must be further addressed before the routine use of multiple IT drugs is advocated.

Ropivacaine.

Ropivacaine (Naropin, AstraZeneca) is a long-acting amide local anaesthetic released for clinical use in 1996. Similar to bupivacaine, ropivacaine is equally effective for s.c. infiltration, epidural and peripheral nerve block for surgery, obstetric and post-operative analgesia. Ropivacaine differs from most other amide-type local anaesthetics in that it is marketed as a pure S-enantiomer, instead of as a racemate. This feature improves the safety of ropivacaine, and, indeed, studies have shown ropivacaine to have less cardiovascular and CNS toxicity than bupivacaine. Ropivacaine is nearly identical to bupivacaine in onset, quality and duration of sensory block, but it produces less motor block. Whether or not the motor sparing effect of ropivacaine is due to a lower relative potency compared to bupivacaine is a matter of intense debate. Despite a better safety profile, the increased cost of ropivacaine may limit its clinical utility.

0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion.

UNLABELLED: We compared the effects of 0.125% ropivacaine with 0.125% bupivacaine in laboring patients using patient-controlled epidural analgesia (PCEA). Fifty-one ASA physical status I or II term parturients with functioning epidural catheters were randomized to receive ropivacaine or bupivacaine using a prospective, double-blind design. Basal infusions (6 mL/h) were supplemented with patient-controlled boluses (5 mL) every 10 min as required. For inadequate analgesia, patients were administered 10-mL boluses of study solution until comfortable. There were no differences in verbal pain scores, amount of local anesthetics used, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction between the two local anesthetics. We conclude that 0.125% ropivacaine and bupivacaine are clinically indistinguishable and are both highly effective for labor analgesia using PCEA. IMPLICATIONS: This study compared labor analgesia from 0.125% ropivacaine and 0.125% bupivacaine using patient-controlled epidural analgesia. We found no significant differences in local anesthetic use, analgesic characteristics, or side effects between 0.125% ropivacaine and 0.125% bupivacaine. We conclude that these two drugs are clinically indistinguishable at this concentration.

Influence of herbicide application to soybeans on soybean cyst nematode egg hatching.

The hatching of Heterodera glycines eggs in soybean root exudates collected after postemergence application of three herbicides, and the hatching potential of H. glycines eggs from females feeding on herbicide-treated plants, were measured in vitro. Hatching in all root exudate solutions (RES) was greater than in deionized water but less than in 0.003 M ZnSO solution. Filtering RES with a 0.22-mum-filter increased H. glycines hatching in RES. Application of acifluorfen, bentazon, and lactofen to foliage of soybean plants inhibited hatching of H. glycines eggs from the same plants. Hatching in RES from the different herbicide-treated soybeans was similar. Application of crop oil concentrate and non-ionic surfactant adjuvant to foliage did not affect hatching of H. glycines eggs from soybean plants.

Glycyl-L-glutamine [beta-endorphin-(30-31)] attenuates hemorrhagic hypotension in conscious rats.

The profound hypotension caused by acute hemorrhage is thought to involve opioid peptide neurons. In this study, we tested whether glycyl-L-glutamine [Gly-Gln; beta-endorphin-(30-31)], a nonopioid peptide derived from beta-endorphin processing, prevents the cardiovascular depression induced by hemorrhage in conscious and anesthetized rats. Previously, we found that Gly-Gln inhibits the hypotension and respiratory depression produced by beta-endorphin and morphine but does not affect opioid antinociception. Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 +/- 2.9 to 56.2 +/- 4.7 mmHg) but did not change heart rate significantly. Intracerebroventricular Gly-Gln (3, 10, or 30 nmol) pretreatment inhibited the fall in arterial pressure and increased heart rate significantly. The response was dose related and was sustained during the 35-min posthemorrhage interval. Pentobarbital sodium anesthesia potentiated the hemodynamic response to hemorrhage and attenuated the effect of Gly-Gln. Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats. These data indicate that Gly-Gln is an effective antagonist of hemorrhagic hypotension.

Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration.

Initial toxicity testing of neostigmine for intrathecal (IT) injection was performed with preservative-free isobaric solution, yet currently available formulations contain the preservatives methyl- and propylparaben and are usually mixed with glucose to yield hyperbaric solutions. Since it has been proposed that preservatives and hyperbaricity increase the risk of neurotoxicity after IT injection, we examined the safety of chronically administered IT neostigmine containing these additives in sheep and rats. Rats receiving daily IT injections of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10 microg, exhibited dose-related antinociception, tremor, and rigidity. In comparison to our previously published study of neostigmine injection in solution without glucose, rats receiving IT neostigmine with glucose displayed less rigidity, tremor, and salivation. Sheep receiving daily injection of glucose alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no histologic evidence of neurotoxicity, nor did they exhibit abnormalities in cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal cord histologic examination in both species revealed fibrosis and inflammation secondary to the catheter without evidence of neuronal damage. These studies support the safety of paraben- and glucose-containing IT neostigmine.

Postoperative analgesia using a low-dose, oral-transdermal clonidine combination: lack of clinical efficacy.

STUDY OBJECTIVE: To determine if a lower than previously reported oral-transdermal clonidine regimen could reduce postoperative morphine requirements without producing systemic side effects. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 29 healthy, ASA physical status I and II females undergoing elective abdominal hysterectomy. INTERVENTIONS: Patients received preoperative oral clonidine 4 to 5 mu/kg and a 7 cm2 transdermal clonidine patch (0.2 mg/24 hours) or a placebo tablet and patch. MEASUREMENTS AND MAIN RESULTS: Postoperative patient-controlled analgesia pumps provided morphine during the 48-hour study period. Morphine use, hemodynamic changes, and nonhemodynamic side effects were recorded. Additionally, visual analog pain scales (VAPS) and plasma concentrations of morphine and clonidine were measured. We found that low-dose clonidine had no potentiating effect on morphine analgesia. Postoperative morphine use, VAPS, and morphine plasma levels were similar between the control and clonidine-treated groups. Nevertheless, patients in the clonidine group experienced a significantly greater incidence of intraoperative and postoperative hypotension and bradycardia than did the control group. No differences were noted in the incidence of nonhemodynamic side effects. CONCLUSIONS: The low-dose oral-transdermal clonidine regimen evaluated failed to reduce postoperative morphine requirements, although patients who received clonidine were still at risk for developing hypotension.

Cyclo(Gly-Gln) inhibits the cardiorespiratory depression produced by beta-endorphin and morphine.

Glycyl-L-glutamine (Gly-Gln; beta-endorphin 30-31) is an endogenous dipeptide that is synthesized through the post-translational processing of beta-endorphin. Previously, we showed that Gly-Gln inhibits the hypotension and respiratory depression produced by central beta-endorphin administration. In this study, we tested whether cyclo(Gly-Gln), a non-polar, cyclic Gly-Gln derivative, was similarly effective following intracerebro-ventricular (i.c.v.) or intra-arterial (i.a.) administration to pentobarbital-anesthetized rats pretreated with beta-endorphin (0.5 nmol i.c.v.). Intracerebroventricular cyclo(Gly-Gln) (0.3, 0.6 or 1.0 nmol) injection produced a dose-dependent inhibition of beta-endorphin-induced hypotension, but not bradycardia, with a potency similar to that of Gly-Gln. Cyclo(Gly-Gln) (5 mg/kg) was also effective following i.a. injection and significantly attenuated the fall in arterial pressure elicited by i.c.v. beta-endorphin, consistent with evidence that cyclic dipeptides permeate the blood-brain barrier; i.a. Gly-Gln was ineffective. Intra-arterial cyclo(Gly-Gln) (5 mg/kg) and i.c.v. Gly-Gln (10 nmol) also attenuated the hypotension and respiratory depression induced by morphine (50 or 100 nmol i.c.v.). Cyclo(Gly-Gln) (0.5, 5.0 or 50.0 mg/kg i.a.) had no effect on arterial pressure or heart rate when given alone. These findings indicate that cyclo(Gly-Gln) is a biologically active peptide capable of reversing the cardiorespiratory depression produced by beta-endorphin or morphine.

Tyrosine hydroxylase in the cerebral ganglia of the American cockroach (Periplaneta americana L.): an immunohistochemical study.

We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the non-glomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons.

Melittin synthesis in the venom system of the honey bee (Apis mellifera L.).

The amount of melittin (measured by a direct hemolytic assay) contained in the venom system of single honey bees (Apis mellifera), of known age, increases from the time of eclosion to an age of about 4 weeks when about 500 micrograms of melittin is present. In older bees (5-6 weeks) the melittin level falls to about 250 micrograms. Measurements of the incorporation of [3H]leucine (injected into the haemolymph) into melittin show that melittin synthesis is most active in bees aged between 1 and 2 weeks after eclosion. The melittin content of the venom system changes as the summer progresses. Melittin levels in a bee of any age greater than 1 week are lower in mid-August than in a bee of the same age in early June.

Autonomic hyperreflexia in a pregnant paraplegic patient. Case report.

BACKGROUND AND OBJECTIVES: Pregnant patients with spinal cord injuries are predisposed to autonomic hyperreflexia, which if unrecognized or untreated can lead to death. Hypertension occurring in laboring patients at risk for autonomic hyperreflexia must be managed aggressively. METHODS: Epidural anesthesia can safely control autonomic hyperreflexia during labor and delivery, but because spinal cord impaired patients lack sensory and motor function below the level of injury, it is difficult to determine the dermatomal spread of epidural anesthesia by the usual methods. This difficulty is highlighted by the following case, reporting an epidural that failed during labor, with the subsequent development of autonomic hyperreflexia. RESULTS: Previously, autonomic hyperreflexia occurring in pregnant patients (undergoing surgical procedures) was treated with intravenous antihypertensive agents. During labor, however, titrating these agents to coincide with uterine contractions is difficult. In this case, epidural anesthesia was repeated and the autonomic hyperreflexia resolved. CONCLUSIONS: Autonomic hyperreflexia can develop in unanesthetized laboring paraplegic patients (failed epidural) but it can be successfully managed with adequate epidural anesthesia.