Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

Glycolysis inhibitors negatively bias blood glucose measurements: potential impact on the reported prevalence of diabetes mellitus.

BACKGROUND: Blood glucose concentrations are essential in defining diabetes mellitus. Recent guidelines advocate either of two discrete methods for sample collection and processing. One of these involves addition of glycolysis inhibitors, such as sodium fluoride-potassium oxalate (NaF-KOx) to sample collection tubes, whereas the other requires immediate refrigeration and sample separation. AIMS: To examine whether the choice of the preanalytical process has any impact on subsequent glucose determinations. METHODS: 62 healthy men participated in the study during screening for diabetes. Paired venous blood samples were collected in a serum-gel tube and a tube containing NaF-KOx (both Sarstedt, Leicester, UK). Serum was promptly separated from gel tube samples and refrigerated, whereas NaF-KOx samples were not separated until immediately before analysis. Glucose concentrations were determined using an Olympus AU 2700 analyser incorporating an automated hexokinase method. RESULTS: Mean (95% CI) glucose concentration in serum-gel tube samples was 5.2 mmol/l (5.0 to 5.4 mmol/l), whereas the concentration in tubes containing NaF-KOx was 4.9 mmol/l (4.8 to 5.1 mmol/l). A negative bias of 0.23 mmol/l (0.16 to 0.30 mmol/l) and relative negative bias of 4.7 % (3.2% to 6.3%) were observed for samples collected in NaF-KOx tubes, consistent with the combined effects of glycolysis and dilution. CONCLUSIONS: Bias associated with the use of NaF-KOx tubes may have a significant impact on the prevalence of fasting hyperglycaemia, according to current diagnostic criteria. The small but significant difference between preanalytical processes should be considered when screening for the presence of diabetes mellitus.

Fatalities caused by the MDMA-related drug paramethoxyamphetamine (PMA).

The past several years have seen a marked increase in the recreational use of 3,4-methylenedioxymethamphetamine (MDMA) or "Ecstasy". MDMA use is especially common among young people participating in dance parties called "raves". Paramethoxyamphetamine (PMA) exhibits both structural and pharmacological similarity to MDMA. It may, however, be a more potent central stimulant, particularly in its effects on serotonergic transmission. Several fatalities from PMA have been reported in Australia, and here we report three recent fatalities that occurred in the midwestern United States in which each of the decedents believed that they were ingesting MDMA. Symptoms observed included agitation and bruxism, progressing to severe hyperthermia, convulsions, and hemorrhage. Blood was screened for drugs of abuse by enzyme immunoassay with the presence of amphetamines indicated in each case. Confirmation and quantitation for amphetamines was performed by gas chromatography-mass spectrometry. The deceased, two males ages 19 and 24 and a female age 18, had postmortem blood PMA concentrations of 1.07, 0.60, and 1.90 mg/L, respectively. PMA is not a contaminant of MDMA, and no MDMA was found in any of these cases. The primary metabolite of PMA is produced by O-demethylation to 4-hydroxyamphetamine, a reaction catalyzed by cytochrome P450 2D6. This enzyme is noted to be genetically polymorphic. Those with the "slow metabolizer" phenotype may be likely to have higher peak blood concentrations of PMA. Whether any of the decedents described herein were of the slow metabolizer phenotype is not known. Several groups have advocated the onsite use of the Marquis Test for the purpose of pill screening in efforts to distinguish PMA from MDMA. A dark purple is consistent with MDMA, whereas PMA imparts no color change in this test. PMA is often in the form of a white pill with a Mitsubishi symbol on one side. This design has been identified in at least one of these fatalities.

Clinical, bacteriologic, serologic, and pathologic features of infections with atypical Taylorella equigenitalis in mares.

OBJECTIVE: To characterize clinical, serologic, bacteriologic, cytologic, and pathologic endometrial responses of mares to 2 donkey-origin atypical bacterial isolates resembling Taylorella equigenitalis. DESIGN: Prospective in vivo study. ANIMALS: 10 healthy mares. PROCEDURE: Mares in estrus (2/group) were inoculated by intrauterine infusion with 2 isolates of classic T equigenitalis or 2 isolates of atypical Taylorella sp or were sham-inoculated. Bacteriologic, serologic, clinical, uterine, cytologic, and pathologic endometrial responses were assessed 4, 11, 21, 35, and 63 days after inoculation and on day 111 in mares with positive culture results on day 63. RESULTS: One atypical isolate failed to cause infection. The second atypical isolate and both classic T equigenitalis isolates induced similar transient metritis and cervicitis. Both classic isolates and 1 atypical isolate induced anti-T equigenitalis complement-fixing antibodies detectable at day 11. Classic isolates and an atypical isolate provoked intense neutrophilic endometritis followed by a resolving, subacute, neutrophilic-mononuclear endometrial response. The atypical isolate and classic isolates were recovered from the uterus, clitoral fossa, or clitoral sinus of one or both exposed mares for as long as 111 days. CONCLUSIONS AND CLINICAL RELEVANCE: Atypical Taylorella sp infections should be considered as a differential diagnosis of equine infertility in US-origin mares, even those not exposed to stallions from countries where contagious equine metritis occurs. The origins and prevalence of atypical Taylorella sp infection in US horses and donkeys are undetermined.

A novel surgical technique for vasectomizing boars.

A novel surgical technique was used for vasectomizing boars. The benefit of this approach over existing methods is that the ductus deferens is isolated prior to its entrance into the spermatic cord, thereby eliminating the potential for damage to associated neurovascular structures that are essential to testicular viability. Additionally, the described surgical procedure can be performed on boars positioned in lateral recumbency. Vasectomized boars can be used in breeding management strategies.

Removal of the caudae epididymides to create infertile boars for use in estrus detection programs.

Epididymectomies (removal of the caudae epididymides) were performed to create infertile boars. The simplicity of this procedure allowed for it to be easily performed on physically or chemically restrained boars that weighted 30 kg. Benefits of the use of epididymectomy, rather than vasectomy, to render boars infertile include low cost, simplicity, reduced surgical time, and minimum need of surgical instruments and materials. Epididymectomized boars are used in swine breeding management programs.

A simple technique for the purification of plasma membranes from ejaculated boar spermatozoa.

Spermatozoa were initially separated from fresh boar ejaculates using a 1.0 M sucrose density gradient. Spermatozoa (1 x 10(8) cells/ml) were subjected to gas cavitation (650 psi, 10 minutes), followed by a 4-step centrifugation technique to yield the final plasma membrane preparation. Purity of the plasma membrane isolate was determined using microscopic techniques (i.e. differential interference contrast and transmission electron microscopy) and marker enzymes for biochemical characterization. Plasma membranes were found to be removed primarily from the periacrosomal region of the sperm. Acrosomes appeared to remain intact on the cavitated spermatozoa. Transmission electron microscopy yielded a homogenous population of 100-200 microns unilamellar vesicles. Enzyme markers specific for plasma, acrosome and mitochondrial membranes substantial the purity observed under visual examination.

Excretion of porcine reproductive and respiratory syndrome virus in semen after experimentally induced infection in boars.

Four boars intranasally inoculated with porcine reproductive and respiratory syndrome (PRRS) virus were monitored for 56 days after exposure for changes in semen characteristics and for the presence of virus in the semen. Clinically, 2 of 4 boars had mild respiratory signs of 1 day's duration after infection. Changes in appetite, behavior, or libido were not detected. All boars seroconverted on the indirect fluorescent antibody and serum virus neutralization tests by day 14 after inoculation. Virus was isolated from serum between days 7 and 14 after inoculation. During the monitoring period, semen volume decreased and pH correspondingly increased; however, this change began 7 to 10 days prior to infection. Differences in sperm morphologic features, concentration, or motility between the preinfection and postinfection samples were not observed. The PRRS virus was detected in semen at the first collection in each of the 4 boars (ie, 3 or 5 days after challenge exposure). Virus was detected in nearly all semen samples collected from the 4 infected boars through days 13, 25, 27, and 43, respectively. Neither gross nor microscopic lesions attributable to PRRS virus were observed in tissues collected at the termination of the experiment (day 56), and virus isolation results from reproductive tissues were negative.

Medically treated miscarriage in Alamance County, North Carolina, 1988-1991.

The authors attempted to identify all medically treated miscarriages in Alamance County, North Carolina, between September 1988 and August 1991. Clinical and demographic characteristics of the cases were evaluated, and risks were calculated in relation to total pregnancies, including induced abortions. Miscarriage cases usually had positive pregnancy tests, and a sizable proportion (66% of whites, 72% of blacks) had a pathology report indicating the presence of a conceptus. Nineteen percent of the cases were identified in hospitals, a more common source for women who were unmarried, young, of low education, and had pregnancies of advanced gestational age. The risk of medically treated miscarriage was 7.7% among whites and 5.5% among blacks, with higher risks among older women. The lower risk among blacks, especially those with lower levels of education, suggests underascertainment, possibly resulting from a failure to seek treatment.

Transoral axial division, under endoscopic guidance, for correction of epiglottic entrapment in horses.

Transoral axial division was performed, using endoscopic guidance, in 20 horses with epiglottic entrapment. Mean age of affected horses was 3 years (range, 2 to 5 years), and there were 18 Standardbreds and 2 Thoroughbreds. Standardbreds and female horses were significantly overrepresented when compared with a reference population. Upper respiratory noise prompted endoscopic examination before surgery in 16 horses, but noise was not heard in 4 horses. Ten horses had entrapment by thin tissue without ulceration, 6 horses had entrapment by thin tissue with small, partial-thickness ulceration, 3 horses had entrapment by moderately thick tissue with large, partial-thickness ulceration, and 1 horse had entrapment with thick tissue and severe ulceration. After surgery, horses received anti-inflammatory medication and box stall rest with hand walking for 7 days. All horses returned to race training on day 7 after surgery and returned to their previous level of racing or training. Epiglottic entrapment recurred in 2 horses (10%), and dorsal displacement of the palate developed in 2 horses after surgery. Relationship of epiglottic entrapment and dorsal displacement of the palate to epiglottic hypoplasia was not apparent. Transoral axial division under endoscopic guidance appeared to be a useful, safe, and economic alternative to currently available methods for management of epiglottic entrapment in horses. Horses with entrapment by thick and ulcerated tissue may be best managed by surgical resection of entrapping tissue.

Fetal dopamine cell survival after transplantation is dramatically improved at a critical donor gestational age in nonhuman primates.

Mesencephalic tissue containing newly generated dopamine neurons was collected from brains of embryonic African green monkeys at 44 and 49 days of gestation and stereotaxically implanted into multiple sites in the caudate nucleus of adult monkeys previously treated with the dopamine protoxin, 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine. Ultrasonography was utilized to assess the developmental stage prior to hysterotomy. Brains were removed for combined histochemical and biochemical analyses at 3 1/2 months after grafting to determine the extent of graft survival and growth. The dopamine content of the target nucleus was assessed from microdissected "punches" placed in proximity to grafts identified in unfixed brain slices prior to fixation. Tissue dopamine levels adjacent to the grafts were elevated markedly, reaching 25-50% of control levels at some sites in the caudate nucleus. Morphometric analysis of graft size and dopamine cell numbers was performed with computer-enhanced, video-based imaging. Exceptionally large grafts that far exceeded their initial size at the time of implantation were seen at each placement site. The dopamine cell count was as high as 3500 in a single graft from E44 tissue, but only as high as 550 from the E49 donor. Up to 15,000 tyrosine hydroxylase-positive neurons were stained in the host monkey that received E44 tissue; only 1/10 as many were seen in each of the recipients of E49 day samples. The earlier donor grafts occupied as much as 15% of the caudate nucleus as seen in a single coronal section; summation of all sections that contained grafts at each placement from the E44 donor revealed average areas occupied by the grafts ranging from 3 to 8% of the caudate nucleus. In comparison, grafts produced from an E49 donor averaged between 2.4 and 5.4% of the area of the target. Qualitatively, grafts from each gestational stage showed well-developed dopamine neurons with morphological characteristics equivalent to those of all three ventral mesencephalic dopamine cell groups. The attainment of large, well-differentiated grafts with thousands of dopaminergic neurons from early gestation tissue suggests that optimal cell survival in primates is dependent on the degree of postgerminal development of the dopamine neuron. Neurite extension may be critical in this regard as well as other, at present, undefined factors. Maximal graft development and cell survival may be a critical element in the ability of neural grafts to reverse a neurological disability and to maintain improvement in the event of continued degeneration of host dopamine neurons.

Episodic scrotal mutilation with concurrent bilateral sperm granuloma in a dog.

Bilateral sperm granuloma with diffuse spermatocele was found to be the cause of infertility in a young Golden Retriever. Anamnesis indicated that the dog had intermittent episodes of self-inflicted ulcerative scrotal dermatitis, beginning when it was 4 to 5 months old and regardless of season or environment. A complete breeding soundness examination produced consistently azoospermic ejaculates in the presence of bilaterally firm, distinct swellings of the epididymides. Because of the poor reproductive prognosis, the owner requested castration and scrotal ablation. Although scrotal trauma was initially thought to be associated with the onset of sperm granuloma formation, evaluation of the history and physical examination and laboratory findings indicated that a bilateral congenital anomaly was the most likely cause of infertility.

Surgical treatment of uterine torsion in a llama (Lama glama).

A multiparous llama was presented because of failure to proceed into the second stage of labor. Clockwise uterine torsion and a live fetus were identified by rectal and vaginal examinations. A cesarean operation was elected because of the prolonged first stage of labor and lack of cervical dilatation. Anesthesia was induced with a 10% guaifenesin solution administered intravenously via a pressurized pump followed by intubation and maintenance with 2% halothane. A ventral midline surgical approach exposed the uterus and the fetus was removed through a uterotomy. The placenta was manually stripped from the myometrial edges of the incision and the margins were oversewn using a continuous interlocking pattern. The uterus was then closed using a continuous Utrecht pattern and the uterus rotated 180 degrees back to its normal anatomical position. The abdomen was closed in 3 layers. Recovery of the llama was uneventful with the male cria able to nurse 6 hours post-operatively. Placental expulsion occurred approximately 48 hours after fetal removal.

Effect of latex and vinyl examination gloves on canine spermatozoal motility.

Two experiments were conducted to determine whether contact with latex or vinyl examination gloves affects canine spermatozoal motility. In experiment 1, semen was collected by digital manipulation from each of 5 dogs, and initial spermatozoal motility was assessed. The ejaculate was divided into 5 equal subsamples of 2 ml each, then randomly assigned to a control group, or treated with a 0.5-cm2 piece of latex or vinyl glove with or without talcum powder. After such exposure, spermatozoal motility was assessed at 1 and 5 minutes. Talcum powder within latex or vinyl glove treatments had no significant effect on spermatozoal motility at either period. Spermatozoal motility in samples did not differ between the control and vinyl glove groups; however, latex glove-treated samples were found to have a significant (P less than 0.05) decrease in spermatozoal motility at 1 and 5 minutes. In experiment 2, the effects of latex and vinyl gloves on canine spermatozoal motility during a sham laboratory manipulation was performed. Three ejaculates of approximately 10 ml were collected from each of 5 dogs and randomly assigned, within each dog, to be either a control (no glove exposure) or allowed to briefly contact either a latex or vinyl glove during sample manipulation. Spermatozoal motility was assessed for each sample immediately prior to and at 1 minute after manipulation. Exposure of semen to latex gloves significantly (P less than 0.05) decreased sample spermatozoal motility, whereas vinyl glove exposure had a minimal (P greater than 0.05) effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroejaculation and artificial insemination in Vietnamese potbellied miniature pigs.

A 15-month-old Vietnamese miniature boar was examined because of suspected infertility. A breeding soundness examination was conducted, using electroejaculation under anesthesia for semen collection. Semen values were normal despite a subpubic location of the testes. Artificial insemination of a gilt with extended semen resulted in the birth of a litter 111 days later. Vietnamese potbellied boars have small and sometimes nearly undetectable scrotal pouches, which may cause the producer to question the fertility of the boars.

Multiple congenital defects in a female calf: a case report.

This case report describes a female calf with arthogryposis, an extra set of incision teeth, ventral abdominal hernia, tibial hemimelia and the nonunion of mullerian ducts. This is possibly the first occurrence of these anomalies in one animal. The cause of these anomalies may have been genetic in origin due to the close relationship between the dam and the sire and the negative history for such various tetragenic factors.

The effects of xylazine and alpha-adrenoreceptor antagonists on bovine uterine contractility in vitro.

The effects of alpha-adrenoreceptor antagonists prazosin (alpha-1), yohimbine (alpha-2), and idazoxan (alpha-2) on xylazine-induced bovine uterine contractility were tested in vitro. Uterine strips from proestrous/estrous and diestrous cows were mounted in tissue baths containing Tyrode's solution. Changes in uterine contractility were measured by strain gauge. The following results were observed: 1) Xylazine increased uterine contractility in a dose dependent manner (cumulative concentrations: 10(-8), 3x10(-8), 10(-7), 3x10(-7) and 10(-6)M). 2) Idazoxan (10(-8), 10(-7) and 10(-6)M) and yohimbine (10(-6), 10(-5) and 10(-4)M) antagonized uterine contractility induced by xylazine in a dose-dependent manner. Idazoxan was approximately 50 to 100 times more potent than yohimbine. 3) Prazosin (10(-5)M) did not alter the effect of xylazine on uterine contractility. These results suggested that xylazine-induced uterine contractility in the cyclic cow is directly mediated by myometrial alpha-2 adrenoreceptors.

Effects of epidural administration of xylazine or lidocaine on bovine uterine motility and perineal analgesia.

The objective of this study was to evaluate and compare the effects of caudal epidural (sacral-coccygeal interspace) administration of xylazine or lidocaine on uterine motility and perineal analgesia in the cow. Six Holstein cows (7 d post estrus) were assigned to one of three treatment groups: control (5 ml saline); lidocaine (0.2 mg/kg, 2% solution); and xylazine (0.06 mg/kg suspended in 5 ml saline), with each cow randomly assigned to each treatment over a period of three estrous cycles. Uterine motility, perineal analgesia, electrocardiography, and overt signs of sedation were recorded. Data were collected at 10-min intervals starting 10 min before treatment and continuing until 60 min post treatment. At 60 min post treatment, oxytocin (20 USP units) was administered i.v. to serve as a positive control for uterine motility. In the xylazine group, uterine motility significantly (P < 0.05) increased at 20 min post treatment, peaked at 30 min, and gradually decreased to non-significant levels at 50 min post treatment when compared with the lidocaine and control groups. Additionally, xylazine produced a higher degree and longer duration of perineal analgesia than lidocaine. Systemically, epidural xylazine produced signs of sedation, salivation, vocalization and bradycardia. Ataxia was also observed in the xylazine-treated group which may have been induced through a local and/or systemic effect. The individual properties of xylazine and lidocaine should be taken into consideration when performing an obstetrical procedure requiring the use of an epidural analgesic agent, and they should be utilized to benefit the clinician in performing the procedure.

Toxicity effects of latex gloves on boar spermatozoa.

It is known that several materials used in semen collection have been found to be detrimental to spermatozoal motility. In this study, examinations for toxic effects of latex and vinyl gloves, used with and without talcum powder on boar spermatozoa, were performed. Ten boars of known fertility with >/=80% sperm motility were divided into two groups (n = 5 boars each) for in vitro and in vivo studies. In the in vitro study, semen was collected from each of the five boars and was divided into five separate aliquots (5 ml each). One aliquot from each of the boars remained as the control, while the remaining aliquots were divided into individual treatments exposing the semen to a l cm(2) piece of latex or vinyl glove with or without talcum powder. In the in vivo experiment, semen from each of the five boars was collected using a gloved hand. During collection, the first half of the sperm-rich fraction was collected into a filtered sterile container, while the second half of the fraction was allowed to run through the palm of either a latex or vinyl powdered glove prior to collection in the container. In both experiments, semen sample motility was assessed by two independent observers at 1 minute after exposure. Results of both experiments consistently showed a significant (P<0.05) effect of latex gloves (with or without talcum powder) on boar semen when compared with the control semen. Motility was at or near 0% at 1 min after exposure to latex. No significant difference (P>0.05) in motility was observed between the control semen and the semen exposed to talcum powdered vinyl gloves. These results show that latex gloves are detrimental to boar spermatozoa. Therefore, it is suggested that when collecting boar semen vinyl gloves should be used.

Farrowing induction with cloprostenol-xylazine combination.

Eighty crossbred, multiparous sows, weighing between 190 and 320 kg, were randomly assigned to the following four treatment groups of 20 sows each: 1) saline-saline, 2) cloprostenol-saline, 3) saline-xylazine and 4) cloprostenol-xylazine. The mean gestation length of each multiparous sow was calculated. Cloprostenol (250 ug/sow, i.m.) or saline was given 3 d prior to the calculated due date at 11:30 a.m. Xylazine (2 mg/kg, i.m.) or saline was given 20 h after either the cloprostenol or previous saline treatment. Cloprostenol-xylazine treated sows had the shortest mean farrowing interval (1.5 +/- 0.3 h) when compared with the rest of the treatment groups (saline-saline:66.0 +/- 8.1, cloprostenol-saline:10.5 +/- 1.9, saline-xylazine:60.6 +/- 5.6 h). Farrowing time, percentage of stillbirths, average birth weight, d-5 and d-21 postbirth weights, number of pigs born, number of pigs born alive, and number of pigs surviving at 5 and 21 d afterbirth were not significantly different among the four groups. This study demonstrated that cloprostenol-xylazine treatment decreases the time to onset of farrowing with less variation than cloprostenol or xylazine alone. Therefore, the use of a cloprostenol-xylazine combination is suggested as an alternative method for inducing farrowing.