Randomized trial comparing ferric carboxymaltose vs oral ferrous glycine sulphate for postoperative anaemia after total knee arthroplasty.

BACKGROUND: Despite preoperative anaemia treatment, a risk of postoperative anaemia remains. This randomized, controlled study evaluated the efficacy of i.v. ferric carboxymaltose (FCM) as postoperative anaemia treatment after total knee arthroplasty (TKA). METHODS: TKA patients with postoperative anaemia [haemoglobin (Hb) 8.5-12.0 g dl(-1)] without prior transfusions were randomly assigned to FCM [700-1000 mg iron (according to calculate iron deficit on postoperative day 2)] or ferrous glycine sulphate (FS; 100 mg iron daily from day 7 onwards) and followed for Hb, iron status, quality-of-life (EQ-5D), and performance (6 min walk test) until day 30. RESULTS: Of 161 preoperatively non-anaemic patients, 122 (75.8%) developed anaemia after operation (within 24 h) and were enrolled in this study (60 FCM, 62 FS). Hb substantially decreased until day 4 in both groups, and partly recovered by day 30. FCM-treated patients achieved Hb ≥12.0 g dl(-1) more frequently (42.3% vs 23.5%; P=0.04) and showed a trend towards higher Hb increase from day 4 to day 30 [+1.7 (1.2) vs +1.3 (1.0); P=0.075] compared with FS-treated patients. Patients with postoperative Hb <10 g dl(-1) experienced better Hb increase with FCM [+2.4 (0.3) g dl(-1)] than FS [+1.1 (0.4) g dl(-1); P=0.018]. Patients being iron-deficient at enrolment (56.7%) had a higher Hb increase with FCM [+1.9 (0.3) g dl(-1)] than FS [+1.2 (0.2) g dl(-1); P=0.03]. Total EQ-5D and performance outcomes were comparable between the groups, but FCM was associated with better scores for 'usual activities'. No i.v. iron-related adverse events were reported. CONCLUSIONS: Preoperatively non-anaemic TKA patients are at high risk of postoperative anaemia. Postoperative i.v. FCM provided significant benefit over oral FS, particularly in patients with preoperative iron deficiency, severe postoperative anaemia, or both. CLINICAL TRIAL REGISTRATION: EudraCT 2010-023038-22; ClinicalTrials.gov NCT01913808.

Severe perioperative anaphylaxis: Incidence in a tertiary hospital in Spain over a 20-year period. A historical cohort study.

OBJECTIVE: To assess the incidence of severe perioperative anaphylaxis, the mechanisms involved, the value of laboratory/skin tests, and the most effective treatments. METHODS: A historical cohort study conducted in a tertiary public hospital in Spain. Patients that had undergone anaesthesia during the 20-year period were included. In these patients, 66 cases of severe anaphylaxis were found. In patients with suspicion of severe anaphylaxis, levels of blood histamine at less than 15min and serum tryptase at 2, 6, and 24h following the reaction were determined. Skin and specific IgE tests were performed between 4 and 8 weeks later. RESULTS: Over the 20-year period, 288 594 anaesthetic procedures were performed. We observed cases of 66 severe anaphylaxis reaction (59% men; age, 60.8±17.3 years. Symptoms observed were cardiovascular (86%), respiratory (73%), and mucocutaneous (56%). Elevated serum tryptase levels were associated with degree of severity at 2 (P<.0001) and 6h (P=.026) and were highest in IgE-mediated reactions (P=.020). All patients required treatment, and 3 events were fatal. In 84.8% of patients, skin and/or specific IgE tests were positive for antibiotics (35.8%), non-steroidal anti-inflammatory drugs (23.1%), neuromuscular blocking agents (15.4%) and latex (15.4%). CONCLUSIONS: The incidence of severe anaphylaxis in our hospital was 1 in 4.373 anaesthetic procedures, with a death rate of 4.5%. All cases required treatment. Serum tryptase was a good predictor of reaction severity. The most frequent causative agents were antibiotics, non-steroidal anti-inflammatory drugs, neuromuscular blocking agents and latex.

The perioperative combination of methadone and ketamine reduces post-operative opioid usage compared with methadone alone.

BACKGROUND: A synergy between ketamine and methadone (ME) to produce antinociception has been demonstrated in experimental neuropathy. We wanted to compare post-operative opioid requirements in patients undergoing multilevel lumbar arthrodesis after the administration combined ME-ketamine (MK) or ME alone. METHODS: This was a randomised double-blind study. During sevoflurane-remifentanil anaesthesia, 11 patients in each group received the following: ketamine bolus (0.5 mg/kg) after tracheal intubation, followed by an infusion of 2.5 µg/kg/min in the MK or saline bolus plus infusion in the ME group. Post-operative analgesia - during 48 h - was provided by patient-controlled analgesia (PCA), delivering bolus containing the following: ME 0.25 mg plus ketamine 0.5 mg in the MK group or ME 0.5 mg in the ME group. Lockout was 10 min, maximum of 3 boluses/h in both groups. Before closing the wound, all the patients received intravenous (i.v.) ME 0.1 mg/kg, dexketoprophen and paracetamol. Pain intensity was evaluated by a numerical rating scale (NRS), on arrival at recovery room (RR) and 24 and 48 h after surgery. In the RR, i.v. ME was administered until NRS was 3 when PCA was started. Dexketoprophen and paracetamol were administered 48 h. RESULTS: Remifentanil requirements were higher in the MK group (P = 0.004). Patients in the MK group received 70% less ME by PCA at 24 h (MK vs. ME group, median and interquartile range) - 3.43 mg (1.9-6.5) vs. 15 mg (9.65-17.38) (P < 0.001) - and at 48 h - 2 mg (0.5-3.63) vs. 9.5 mg (3.5-13.75) (P = 0.001). Patients in the MK group also attempted less doses, at 24 h: 19.5 (12.75-79.5) vs. 98 (41.5-137) (P = 0.043). Both groups had similar NRS values and comparable side effects. CONCLUSIONS: Perioperative ketamine-ME combination significantly decreased opioid consumption by PCA.

[Acute coronary syndrome during a cesarean section in a healthy young woman]. / Síndrome coronario agudo durante una cesárea en mujer joven sana.

Acute coronary syndrome (ACS) during pregnancy and delivery is a rare event that is usually related to prior disease or family history. Factors that contribute to the appearance of ACS during delivery in women with healthy coronary arteries include high doses of drugs to suppress contractions or increase uterine muscle tone and cardiovascular instability of any kind. Clinical and electrocardiographic abnormalities (eg, ST segment depression) that are suggestive of ACS have been reported to occur during cesarean section but without subsequent enzyme or echocardiographic abnormalities.

Dexmedetomidine in difficult airway management with a fibre-optic bronchoscope in the awake patient with Klippel-Feil Syndrome. / Dexmedetomidina en el manejo de la vía aérea difícil con fibrobroncoscopio en paciente despierto afecto de síndrome de Klippel-Feil.

Klippel-Feil Syndrome is a disease characterised by congenital fusion of cervical vertebra, which leads to cervical limitation and instability. In these cases, the best option is the orotracheal intubation with the fibre-optic bronchoscope with the patient awake. The advantage is that cervical movements that could lead to neurological damage are minimised. In these patients, adequate sedation, together with instillation of local anaesthetic in the pharynx and hypopharynx, is the key to reducing patient discomfort and achieving successful orotracheal intubation. Dexmedetomidine is a selective α2- adrenergic receptor agonist that produces sedation and analgesia at the locus coeruleus without producing respiratory depression, as well as maintaining patient collaboration. The case is presented of a patient with Klippel-Feil Syndrome and difficult airway management, who was given a dexmedetomidine infusion at 0.6µg/kg/h as sedation for an awake fibre-optic endotracheal intubation.

Anaesthesia management in epilepsy surgery with intraoperative electrocorticography. / Manejo anestésico en la cirugía de epilepsia con electrocorticografía intraoperatoria.

Epilepsy surgery is a well-established treatment for patients with drug-resistant epilepsy. The success of surgery depends on precise presurgical localisation of the epileptogenic zone. There are different techniques to determine its location and extension. Despite the improvements in non-invasive diagnostic tests, in patients for whom these tests are inconclusive, invasive techniques such intraoperative electrocorticography will be needed. Intraoperative electrocorticography is used to guide surgical resection of the epileptogenic lesion and to verify that the resection has been completed. However, it can be affected by some of the anaesthetic drugs used by the anaesthesiologist. Our objective with this case is to review which drugs can be used in epilepsy surgery with intraoperative electrocorticography.

Density spectral array of BIS VISTA™ monitoring system in a functional hemispherectomy. / Monitorización con espectrograma del sistema de monitorización BIS VISTA™ en una hemisferectomía funcional.

We present the case of an adult patient with drug-resistant epilepsy caused by extensive inflammation in the right cerebral hemisphere. She was scheduled to undergo right functional hemispherectomy, which is common in pediatric surgery, but about which few studies have been published with respect to adult patients. During the intraoperative period, the density spectral array of the bilateral bispectral index (BIS) VISTATM monitoring system was used. We observed a power increase in low frequency (0.1-4Hz) and alpha bands (8-12Hz) in the right hemisphere, where the epileptogenic focus was. During disconnection from the frontal lobe, there was a marked decrease of power in low frequency and alpha bands on the right side, with no changes during disconnection from other areas of the brain. We think that further studies are needed to determine whether the density spectral array can be a useful tool for monitoring the effectiveness of functional hemispherectomy.

[Sedation and analgesia with propofol plus low-dose ketamine for retrobulbar block]. / Sedoanalgesia con propofol-ketamina a bajas dosis para la práctica del bloqueo retrobulbar.

OBJECTIVES: To determine if adding ketamine to propofol provides better sedation than propofol alone for patients receiving a retrobulbar block for eye surgery. MATERIAL AND METHODS: Randomized double-blind trial enrolling 50 patients receiving a retrobulbar nerve block for eye surgery. Patients were randomly assigned to 2 groups. In the propofol group sedation was induced with 0.45 mg x kg(-1) of propofol. In the ketamine plus propofol group sedation was induced with 0.45 mg x kg(-1) of propofol plus 0.25 mg x kg(-1) of ketamine. We recorded patient characteristics (age, weight, ASA class, height, sex), hemodynamic variables (blood pressure, heart rate), puncture conditions, sedation (score on the Observer's Assessment of Alertness/Sedation [OAA/S] scale), ventilation (end-tidal carbon dioxide pressure, apneas, need for reanimation maneuvers, pulse oximetry), time until onset of effect, duration of effect, and amnesia. RESULTS: No significant differences were observed in time to onset, duration of effect, patient characteristics, hemodynamic or respiratory variables, or amnesia. Sedation assessed on the OAA/S-scale was lower in the propofol group and the puncture conditions were significantly better in the ketamine plus propofol group. The only adverse psychomimetic reaction was transient agitation, observed in 2 propofol group patients. CONCLUSIONS: Low doses of ketamine associated with propofol improve puncture conditions for performing a retrobulbar block without increasing unwanted side effects.

The T cell death knell: immune-mediated tumor death in renal cell carcinoma.

The antitumor effect of T cells is executed either through CD95 or Perforin (PFN)/Granzyme B (GrB) pathways. Induction of apoptosis by either mode requires activation of caspase family members. However, recent studies have suggested that cell death can proceed in the absence of caspase induction and apoptotic events. We investigated the contribution of CD95 and PFN/GrB-mediated cytotoxicity to apoptotic and necrotic mechanisms of cell death in human renal cell carcinoma. Although freshly isolated and cultured tumors expressed CD95 on their surface, they were resistant to CD95-mediated apoptosis. CD95 resistance coincided with decreased levels of FADD protein and diminished caspase-3-like activity. In contrast, we demonstrated that tumor cell death mediated by PFN/GrB can be achieved in the absence of functional caspase activity and is accompanied by a dramatic accumulation of nonapoptotic necrotic cells.

Interferon-gamma and CXC chemokine induction by interleukin 12 in renal cell carcinoma.

Interleukin 12 (IL-12) is known to play an important role in the development of an antitumor response. Its activity has been shown to be dependent upon the intermediate production of IFN-gamma and the influx into the tumor of CD8 lymphocytes. In a murine model, tumor regression induced by IL-12 treatment correlated with IFN-gamma, IP-10, and Mig expression in the tumor bed and was abrogated by antibodies to both chemokines. Here we examined the effects of rHuIL-12 on IFN-gamma and CXC chemokine gene expression in patients with renal cell carcinoma (RCC) in an attempt to determine whether a similar series of molecular events leading to IL-12-mediated tumor regression in mice is also detectable in humans. As in the murine RENCA model, cultured RCC cells themselves could be induced by IFN-gamma to synthesize IP-10 and Mig mRNA. Explanted RCC produced IFN-gamma and IP-10 mRNA in response to IL-12 treatment, which was consistent with the finding that biopsied RCC tumors from IL-12-treated patients also variably expressed augmented levels of those molecules after therapy. Although Mig mRNA was present in the majority of biopsied tumors prior to treatment, both the Mig and IP-10 chemokines as well as IFN-gamma were induced in the peripheral blood mononuclear cells of IL-12-treated patients. Skin biopsies of IL-12-treated patients also all synthesized IP-10 mRNA. This study demonstrates that recombinant human IL-12 therapy of patients with RCC has the potential to induce the expression of gene products within the tumor bed that may contribute to the development of a successful antitumor response.

Mechanisms of apoptosis in T cells from patients with renal cell carcinoma.

Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results from several laboratories suggest that FasL (L/CD95L) expression in tumors may be responsible for this process. In this study of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional because in coculture experiments, FasL+ tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an effective T-cell-mediated antitumor response.

[Therapeutic approach to postoperative anemia]. / Aproximación terapéutica a la anemia postoperatoria.

Postoperative anemia is a common finding in patients who undergo major surgery, and it can affect early rehabilitation and the return to daily activities. Allogeneic blood transfusion is still the most widely used method for restoring hemoglobin levels rapidly and effectively. However, the potential risks of transfusions have led to the review of this practice and to a search for alternative measures for treating postoperative anemia. The early administration of intravenous iron appears to improve the evolution of postoperative hemoglobin levels and reduce allogeneic transfusions, especially in patients with significant iron deficiency or anemia. What is not clear is whether this treatment heavily influences rehabilitation and quality of life. There is a lack of well-designed, sufficiently large, randomized prospective studies to determine whether postoperative or perioperative intravenous iron treatment, with or without recombinant erythropoietin, has a role in the recovery from postoperative anemia, in reducing transfusions and morbidity rates and in improving exercise capacity and quality of life.

Meconium-stained amniotic fluid in labor: a randomized trial of prophylactic amniofusion.

OBJECTIVES: To investigate the effect of amnioinfusion in women with meconium-stained amniotic fluid on the rate of cesarian sections and on neonatal morbidity. STUDY DESIGN: A randomized controlled trial. A total of 206 women with meconium-stained amniotic fluid were assigned to receive amnioinfusion via two-way catheter or no amnioinfusion (control group). The catheter was inserted and other treatment was the same in both groups. RESULTS: Amnioinfusion decreased the rate of cesarian sections for fetal distress (RR 0.23, 95% CI 0.07-0.79) and increased mean pH at birth (7.24+/-0.1 versus 7.21+/-0.1, P<0.05). It also decreased the frequency of variable fetal heart rate decelerations (RR 0.74, 95% CI 0.59-0.92), and of meconium below the vocal cords in neonates (RR 0.37, 95% CI 0.19-0.69). CONCLUSIONS: Amnioinfusion improves the neonatal outcome and reduces the frequency of cesarian sections.

Sex differences in serum hormone levels in umbilical vein blood.

OBJECTIVE: To determine the serum levels of FSH, LH, PRL, estradiol, progesterone and testosterone in umbilical vein blood in a group of normal neonates. METHOD: Umbilical vein blood was obtained for serum analyses from 52 newborns (25 females and 27 males) in the Maternity of the Hospital Regional Virgen de las Nieves, Granada (Spain) and means were compared with Student's t-test. RESULT: Mean values of prolactin, estradiol and progesterone were similar in both sexes. The levels of gonadotropins in umbilical vein blood found were significantly higher in newborn males than in females (P < 0.001 for LH, P < 0.007 for FSH). Testosterone levels were higher in male neonates than in females (P < 0.004). CONCLUSION: Our data reflect the dynamic state of male fetal endocrinological status in comparison to female fetuses, and strongly suggest that the mechanisms of hormonal regulation differ in the two sexes.

[Severe anaphylactic reaction to metamizol during subarachnoid anesthesia]. / Reacción anafiláctica grave al metamizol durante una anestesia subaracnoidea.

A 59-year-old man with no relevant medical history underwent a right saphenectomy under subarachnoid anesthesia with mepivacaine. Administration of intravenous metamizol for postoperative analgesia was followed by severe anaphylactic reaction with respiratory failure and ventricular fibrillation. The patient recovered after orotracheal intubation and defibrillation. High serum tryptase levels 2 and 6 hours after the episode and positive skin prick tests confirmed the diagnosis of anaphylactic reaction mediated by immunoglobulin-E antibodies. Anaphylactic reactions to metamizol may be more common than would appear based on reports in the literature. When signs present suddenly with cardiovascular or respiratory involvement, symptomatic treatment should be started even in the absence of cutaneous or mucosal signs and allergy tests should be carried out immediately.