Results at 3-year follow-up of totally extraperitoneal (TEP) hernia surgery with long-term resorbable mesh.

INTRODUCTION: Synthetic non-resorbable mesh is almost standard in hernia surgery. However, several studies have showed negative effects of permanent implants such as chronic inflammation and complications involving different organs bordering the mesh. Such complications can raise the risk of chronic post-operative pain (CPP). Recently promising results regarding CPP have been published in patients with Lateral Inguinal Hernia (LIH) using a slowly resorbable mesh in Lichtenstein technique. For this reason the aim of the present study was to find the effect of a slowly resorbable implant on the long-term rate of hernia recurrence and chronic post-operative pain in patients with LIH repaired with TEP procedure. METHODS: Prospective pilot study of TEP repair using TIGR® Matrix Surgical Mesh in 35 primary LIH. At 3-year follow-up the Visual Analogue Scale (VAS) and the Inguinal Pain Questionnaire were employed to assess pain. Recurrence was determined by ultrasound and clinical examination. RESULTS: All patients completed the pain questionnaires but one patient did not attend the planned clinical examination for the 3-year follow-up. No patients had CPP, as defined in the World Guidelines for Groin Hernia Management. Almost all patients had lower VAS score in any activity 3 years following surgery in comparison to the preoperative period. Three patients (8.8%) suffered symptomatic recurrence during the 3-year follow-up. CONCLUSION: TEP repair in patients with LIH using a synthetic long-term resorbable mesh was found to be encouraging respecting chronic post-operative pain at 3-year follow-up but at the cost of an increased risk of recurrence.

Management of post-partum haemorrhage.

Management of post-partum haemorrhage (PPH) involves the treatment of uterine atony, evacuation of retained placenta or placental fragments, surgery due to uterine or birth canal trauma, balloon tamponade, effective volume replacement and transfusion therapy, and occasionally, selective arterial embolization. This article aims at introducing pregnancy- and haemorrhage-induced changes in coagulation and fibrinolysis and their relevant compensatory mechanisms, volume replacement therapy, optimal transfusion of blood products, and coagulation factor concentrates, and briefly cell salvage, management of uterine atony, surgical interventions, and selective arterial embolization. Special attention, respective management, and follow-up are required in women with bleeding disorders, such as von Willebrand disease, carriers of haemophilia A or B, and rare coagulation factor deficiencies. We also provide a proposal for practical instructions in the treatment of PPH.

The influence of ondansetron on the analgesic effect of acetaminophen after laparoscopic hysterectomy.

The 5-HT(3) antagonists tropisetron and granisetron have been shown to block the analgesic effect of acetaminophen in healthy volunteers. To study the interaction between ondansetron and acetaminophen in women undergoing laparoscopic hysterectomy, we randomized 134 patients into three groups to receive acetaminophen-placebo (AP), acetaminophen-ondansetron (AO), or placebo-placebo (PP). One gram of intravenous acetaminophen or placebo was administered at the induction of anesthesia and every 6 h thereafter for 24 h, and 4 mg of ondansetron or placebo was administered at the end of surgery. Pain control was provided by patient-controlled analgesia (PCA)-oxycodone. Acetaminophen (as compared to placebo) in periodic doses starting at induction of anesthesia reduced the total dosage of oxycodone required over 0-24 h (P = 0.031), but ondansetron given at the end of the surgery had no impact on the analgesic effect of acetaminophen (P = 0.723). The Numeric Rating Scale (NRS) scores for pain were similar whether ondansetron or placebo was administered at the end of the surgery. Therefore, it may be concluded that in women undergoing laparoscopic hysterectomy, the administration of periodic doses of intravenous acetaminophen (as compared to placebo) starting at induction of anesthesia reduces the total dose requirement of oxycodone, and a concomitant dose of a 5-HT(3) antagonist such as ondansetron at the end of the surgery does not block the analgesic effect of acetaminophen.

Is persistent visual neglect associated with poor survival?

BACKGROUND: The association of visual neglect with survival after right hemisphere (RH) stroke has received only limited attention. OBJECTIVE: This study explores the relationship of visual neglect and its spontaneous recovery to survival in a homogenous patient group with first-ever RH stroke. METHODS: Fifty-one RH stroke patients who suffered an infarct between 1994 and 1997 were retrospectively followed for survival until August 31, 2009. Acute-phase neurological, neuropsychological and neuroradiological data were studied to identify predictors of survival. RESULTS: Twenty-eight patients died during the follow-up. Age, education, and poor recovery of visual neglect emerged as significant single predictors of death. The best set of predictors for poor survival in the multivariate model was poor recovery of visual neglect and low education. CONCLUSIONS: Poor recovery of visual neglect is associated with long-term mortality in RH infarct patients. The follow-up of RH patients' neuropsychological performance gives additional information about the prognosis.

PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease.

Variant Alzheimer's disease (VarAD) with spastic paraparesis and presenile dementia is associated with certain mutations of the presenilin 1 (PS-1) gene, particularly those leading to deletion of exon 9 (PS-1Delta E9). VarAD is neuropathologically characterized by the presence of unusually large, Abeta42 positive, non-cored 'cotton wool' plaques (CWPs), also devoid of dystrophic neurites. The aim of the present study was to find out whether [(11)C]PIB would show increased uptake and serve as an in vivo biomarker of amyloid accumulation in VarAD. A further aim was to assess the correspondence of the [(11)C]PIB binding to the amount and type of Abeta deposits in another group of deceased VarAD patients' brains. We studied four patients with VarAD and eight healthy controls with PET using [(11)C]PIB as tracer. Parametric images were computed by calculating the region-to-cerebellum and region-to-pons ratio in each voxel over 60-90 min. Group differences in [(11)C]PIB uptake were analysed with automated region-of-interest (ROI) analysis. [(11)C]PIB uptake was compared to the immunohistochemically demonstrated deposition of Abeta in the brains of another group of four deceased VarAD patients. Patients with VarAD had significantly higher [(11)C] PIB uptake than the control group in the striatum (caudate nucleus and putamen), anterior and posterior cingulate gyrus, occipital cortex and thalamus. In the caudate and putamen [(11)C]PIB uptake, expressed as region-to-cerebellum ratio, was on the average 43% greater than the mean of the control group. The increases in the anterior (28%) and posterior (27%) cingulate gyrus, occipital cortex (21%) and thalamus (14%) were smaller. All VarAD patients showed this similar topographical pattern of increased [(11)C]PIB uptake. The results were essentially similar when the uptake was expressed as region-to-pons ratios. [(11)C]PIB imaging shows increased uptake in patients with VarAD especially in the striatum, and it can be used to detect amyloid accumulation in vivo in these patients. The pattern of increased [(11)C]PIB uptake is different from that described in sporadic Alzheimer's disease and resembles that seen in Alzheimer's disease patients with certain presenilin-1 mutations or amyloid precursor protein gene duplication showing predominantly striatal increase in [(11)C]PIB uptake.

Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.

BACKGROUND: Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally. METHODS: Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1-8 and 1-24 h after surgery. RESULTS: The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1-8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups. CONCLUSIONS: Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required.

Midazolam and other benzodiazepines.

The actions of benzodiazepines are due to the potentiation of the neural inhibition that is mediated by gamma-aminobutyric acid (GABA). Practically all effects of the benzodiazepines result from their actions on the ionotropic GABA(A) receptors in the central nervous system. Benzodiazepines do not activate GABA(A) receptors directly but they require GABA. The main effects of benzodiazepines are sedation, hypnosis, decreased anxiety, anterograde amnesia, centrally mediated muscle relaxation and anti-convulsant activity. In addition to their action on the central nervous system, benzodiazepines have a dose-dependent ventilatory depressant effect and they also cause a modest reduction in arterial blood pressure and an increase in heart rate as a result of a decrease of systemic vascular resistance. The four benzodiazepines, widely used in clinical anaesthesia, are the agonists midazolam, diazepam and lorazepam and the antagonist flumazenil. Midazolam, diazepam and flumazenil are metabolized by cytochrome P450 (CYP) enzymes and by glucuronide conjugation whereas lorazepam directly undergoes glucuronide conjugation. CYP3A4 is important in the biotransformation of both midazolam and diazepam. CYP2C19 is important in the biotransformation of diazepam. Liver and renal dysfunction have only a minor effect on the pharmacokinetics of lorazepam but they slow down the elimination of the other benzodiazepines used in clinical anaesthesia. The duration of action of all benzodiazepines is strongly dependent on the duration of their administration. Based on clinical studies and computer simulations, midazolam has the shortest recovery profile followed by lorazepam and diazepam. Being metabolized by CYP enzymes, midazolam and diazepam have many clinically significant interactions with inhibitors and inducers of CYP3A4 and 2C19. In addition to pharmacokinetic interactions, benzodiazepines have synergistic interactions with other hypnotics and opioids. Midazolam, diazepam and lorazepam are widely used for sedation and to some extent also for induction and maintenance of anaesthesia. Flumazenil is very useful in reversing benzodiazepine-induced sedation as well as to diagnose or treat benzodiazepine overdose.

Fluctuation in spontaneous recovery of left visual neglect: a 1-year follow-up.

Spontaneous recovery and possible fluctuation in left visual neglect, and its relation to stroke severity, basic activities of daily living (ADL) and extended ADL were examined at 10 days, at 3, 6, and 12 months after onset. Twenty-one of 56 right hemisphere stroke patients had visual neglect. Three visual neglect recovery groups were identified: continuous, fluctuating and poor recovery. We concentrated on the comparison of the continuous and the fluctuating recovery groups. At the acute phase the fluctuating recovery group had larger infarcts, more severe neglect and stroke, and a lower level of basic ADL compared to the continuous recovery group. In the continuous recovery group stable recovery was detected up to 6 months, whereas in the fluctuating recovery group recovery was incoherent in neglect and in extended ADL. A minimum follow-up period of 6 months including the evaluation of extended ADL is recommended for neglect patients due to possible fluctuation in visual neglect.

An open non-randomized study of recombinant activated factor VII in major postpartum haemorrhage.

BACKGROUND: Empirical off-label use of recombinant activated factor VII (rFVIIa) has been reported to be effective in some cases of severe postpartum haemorrhage (PPH). Successful management of these patients has lead to more wide-spread use of rFVIIa in less severe cases without any evidence for the advantages of its administration. METHODS: Until November 2006, we had administered rFVIIa to 38 parturients. Based on our initial experience with the first 12 patients, we prepared guidelines for the use of rFVIIa. During the existence of these guidelines, we made a retrospective comparison of the 26 women who received rFVIIa with another 22 women who were treated during the same time period without using rFVIIa. RESULTS: The total amount of blood loss was significantly higher (11.3 +/- 4.5 vs. 8.0 +/- 3.1 l), and the coagulation screen revealed significantly longer partial thromboplastin time (APTT) and prothrombin time (PT) values and significantly lower fibrinogen values in patients receiving rFVIIa. The need for red blood cells, platelets and fibrinogen concentrate was significantly higher in these women. Although the response was considered good in two-thirds of the women, several patients received rFVIIa with a poor or no response as a result of arterial bleeding. CONCLUSION: The decision to use rFVIIa resulted from a more profound haemorrhage. We did not gain any evidence to extend the use of rFVIIa into less severe cases of PPH. Furthermore, this policy would result in a profound increase in the overall costs of the treatment. Randomized placebo-controlled trials are urgently needed to optimize the use of rFVIIa in obstetric haemorrhage.

Transfusion of red blood cells: no impact on length of hospital stay in moderately anaemic parturients.

BACKGROUND: In a search for information to improve decision making on red blood cell (RBC) transfusion, we examined the impact of RBC transfusion on the length of hospital stay for delivery in moderately anaemic women (haemoglobin, 7-10 g/dl). METHODS: This was a retrospective, observational study covering 2 years (2002 and 2003), and included major blood-transfusing hospitals from four university and five central hospital districts managing 67.5% of Finnish in-hospital deliveries. The impact of the transfusion of 1-2 RBC units vs. no transfusion on the length of hospital stay was evaluated for three different haemoglobin levels: 7-7.9, 8-8.9 and 9-10 g/dl. RESULTS: Of the 1954 moderately anaemic mothers in hospital for delivery, 13.3% were transfused with RBC. The mean length of hospital stay was 5.2 days vs. the average Finnish hospital delivery stay of 3.5 days. No differences in stay were found between patients with comparable anaemia transfused with 1-2 RBC units or none (at the three haemoglobin levels: P= 0.50, P= 0.07 and P= 0.54, respectively). The final haemoglobin value was higher (P < 0.001) in transfused patients. CONCLUSION: The duration of admission for delivery in moderately anaemic parturients was longer than the average length of hospital stay in Finnish parturients. However, 1-2 RBC units had no impact on the length of stay, suggesting that unnecessary RBCs are transfused after delivery. Thus, transfusion practices in obstetrics are not always optimal.

Surgical stress index reflects surgical stress in gynaecological laparoscopic day-case surgery.

BACKGROUND: Monitoring of analgesia remains a challenge during general anaesthesia. The surgical stress index (SSI) is derived from the photoplethysmographic waveform amplitude and the heart beat-to-beat interval. We evaluated the ability of SSI to measure surgical stress in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping State Entropy (SE) at a predetermined level, SSI would be higher in patients receiving a beta-blocking agent (esmolol) than in those receiving an opioid (remifentanil) during laparoscopy. METHODS: Thirty women undergoing gynaecological laparoscopy were assigned randomly to receive esmolol (n = 15) or remifentanil (n = 15). Anaesthesia was induced with propofol and fentanyl and maintained with desflurane and nitrous oxide 50% in oxygen to keep SE at 50(5). The infusion of esmolol or remifentanil was started before laparoscopy and adjusted to keep the systolic blood pressure at -20 to +10% from the preoperative value. RESULTS: During the fentanyl phase, before surgery, both groups behaved similarly, with an increase in SSI after intubation. In the patients receiving esmolol, the SSI reacted to the initial incision (P < 0.05), and remained high after trocar insertion (P < 0.05). In patients receiving remifentanil, it did not react to the initial incision, but increased after trocar insertion (P < 0.05), and it remained lower both after incision (P < 0.05) and after trocar insertion (P < 0.05). CONCLUSION: SSI was higher in patients receiving esmolol. The index seems to reflect the level of surgical stress and may help guide the use of opioids during general anaesthesia.

Premedication with controlled-release oxycodone does not improve management of postoperative pain after day-case gynaecological laparoscopic surgery.

BACKGROUND: Controlled-release (CR) oxycodone provides an option for the prevention of postoperative pain. We designed this randomized double-blinded placebo controlled study to evaluate the control of pain after premedication with CR oxycodone 15 mg in addition to ibuprofen 800 mg orally in day-case gynaecological laparoscopic surgery. METHODS: Sixty consenting patients were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day in combination with fentanyl i.v. in the recovery room and normal-release (NR) oxycodone orally after the recovery room. The visual analogue scale (VAS) scores for pain and side-effects, and the amounts of postoperative analgesics were recorded for 24 h after discharge from the hospital. After a statistical analysis of the original study, we extended the study to investigate another 10 patients, who received CR oxycodone 15 mg orally in an open-labelled fashion 60 min before surgery. The plasma concentrations of oxycodone were measured from samples drawn before and 2, 4, 6 and 8 h after premedication. RESULTS: The amounts of fentanyl [100 microg (0-330) in the CR oxycodone group; 125 microg (0-330) in the placebo group], NR oxycodone, or the VAS scores for pain during the first 24 h after the discharge from the hospital did not differ after the premedication with CR oxycodone or placebo. In the extension study group, the peak plasma concentration (C(max)) of oxycodone was 10.0 (4.6-14.7) ng ml(-1), indicating possibly a sub-therapeutic level. CONCLUSION: Oral premedication with CR oxycodone did not improve management of postoperative pain after day-case gynaecological laparoscopic surgery.

Response Entropy is not more sensitive than State Entropy in distinguishing the use of esmolol instead of remifentanil in patients undergoing gynaecological laparoscopy.

BACKGROUND: Monitoring of analgesia remains a challenge during general anaesthesia. Activation of Response Entropy (RE) to painful stimuli has been suggested to be a sign of inadequate analgesia. We evaluated the ability of RE to be more sensitive than State Entropy (SE) in measuring nociception in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping SE at a predetermined level, RE would be higher in patients receiving a beta-blocking agent (esmolol) instead of an opioid (remifentanil) during a propofol/nitrous oxide anaesthesia. METHODS: Fifty-one women aged between 22-53 years were randomly assigned to receive esmolol (n=25) or remifentanil (n=26). SE was kept at 50+/-5. RE and SE were recorded at an interval of 30 s to 2 min and the areas under the RE and SE value-time curves (AUCRE and AUCSE) were calculated during the time of intubation and start of surgery as well as during the entire anaesthesia. The difference between RE and SE recordings in both groups was determined by subtracting the AUCSE from the corresponding AUCRE. Movements of the patients were recorded. RESULTS: No significant differences were detected in any of the several AUC values between the groups. The difference between RE and SE recordings was similar in both groups. Every patient in the esmolol group moved some time during the procedure interfering with surgery while no one in the remifentanil group moved. CONCLUSION: In patients undergoing gynaecological laparoscopic day-case surgery, RE seems not to be more sensitive than SE in guiding the use of opioids during general anaesthesia.

Effect of ciprofloxin on the pharmacokinetics of intravenous lidocaine.

BACKGROUND AND OBJECTIVE: Recent studies have suggested that cytochrome P-450 isoenzyme 1A2 has an important role in lidocaine biotransformation. We have studied the effect of a cytochrome P-450 1A2 inhibitor, ciprofloxacin, on the pharmacokinetics of lidocaine. METHODS: In a randomized, double-blinded, cross-over study, nine healthy volunteers ingested for 2.5 days 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 1.5 mg kg[-1] lidocaine intravenously over 60 min. Plasma concentrations of lidocaine, 3-hydroxylidocaine and monoethylglycinexylidide were determined for 11 h after the start of the lidocaine infusion. RESULTS: Ciprofloxacin increased the mean peak concentration and area under plasma concentration-time curve of lidocaine by 12% (range [-6] to+46%; P<0.05) and 26% (8--59%; P 0.01), respectively. The mean plasma clearance of lidocaine was decreased by ciprofloxacin by 22% (7--38%; P<0.01). Ciprofloxacin decreased the area under the plasma concentration-time curve of monoethylglycinexylidide by 21% (P<0.01) and that of 3-hydroxylidocaine by 14% (P< 0.01). CONCLUSION: The plasma decay of intravenously administered lidocaine is modestly delayed by concomitantly administered ciprofloxacin. Ciprofloxacin may increase the systemic toxicity of lidocaine.

De novo seropositive rheumatoid arthritis during immunosuppressive treatment after kidney transplantation.

We detected de novo seropositive erosive rheumatoid arthritis (RA) in a patient seven years after successful cadaveric kidney transplantation (RTx). RA developed in spite of treatment with cyclosporine A (CyA), methylprednisolon (MP) and azathioprine (Aza), compounds often also used for treatment of active RA. Renal failure was due to diabetes mellitus (DM) nephropathy. Besides a slight increase in C-reactive protein (CRP) concentration two years after RTx, the clinical symptoms of RA were observed seven years after RTx. RA was confirmed by X-ray examination, isotopic skeletal scan and positive serum RA factor. After switching Aza to methotrexate (Mtx) treatment, his symptoms disappeared and CRP concentration returned to normal. Our patient had HLA DRB1 *0101, *0401 alleles and DQB1 *0501, *0302 alleles which have strong genetic association with both DM and RA. To our best knowledge, this is the first case in which de novo seropositive erosive RA developed while on treatment with triple immunosuppression after RTx. The immunosuppressive treatment probably masked the inflammation and symptoms of RA.

Recombinant factor VIIa for life-threatening post-partum haemorrhage.

The treatment of life-threatening post-partum haemorrhage (PPH) still remains challenging, and hysterectomy may be required to control the bleeding. We present 12 cases of severe PPH treated with recombinant factor VIIa (rFVIIa). We briefly describe the causes of the haemorrhage and the medical and surgical interventions before rVIIa administration. In 11 women there was a partial or good response to rFVIIa administration, while in one there was no response. In the four women undergoing a subsequent selective arterial embolization, the bleeding was significantly reduced although not completely stopped. From our experience with these 12 cases, and from previously reported cases, the use of rFVIIa may be of benefit in life-threatening PPH. However, treatment with rFVIIa, in addition to standard surgical and medical interventions, may not be definitive in every patient and a selective arterial embolization may be needed.

Brain injury after adult cardiac surgery.

Despite remarkable progress in surgical, cardiopulmonary bypass and anaesthetic techniques during the last three decades, brain damage remains an important complication of adult cardiac surgery. Effective brain protection strategies are already implemented today, but ongoing research is needed to meet the challenges faced in operating on increasingly old and disabled patients. The incidence of brain injury may be reduced by modifying the surgical procedure according to carotid duplex scanning and epiaortic echocardiography, by using techniques to reduce microembolization during cardiopulmonary bypass and by optimizing patient temperature during and after surgery. Increased knowledge will aid in choosing the best procedure or combination of procedures in each case to ensure that risks do not outweigh benefits.

No effect of cardiopulmonary bypass on hypnosis in patients anaesthetized with propofol and alfentanil.

BACKGROUND: The effect of cardiopulmonary bypass (CPB) on the level of anaesthetic depth has not been studied previously in a randomized way. METHODS: We assessed the effect of CPB on the propofol needed to maintain a fixed bispectral index score, and on the recovery from anaesthesia in 22 patients undergoing coronary artery bypass graft surgery with CPB (on-pump) compared with 18 patients operated on without CPB (off-pump). Anaesthesia was induced and maintained with propofol and alfentanil. Throughout the procedure, the infusion rate of propofol was adjusted to keep the BIS value at 40 +/- 5. RESULTS: With the off-pump technique, the duration of surgery and anaesthetic administration were significantly greater. The need for propofol in proportion to time was exactly the same in both groups. During anaesthesia and the first 3 h thereafter, the BIS recordings were similar in both groups. No differences were detected in the time to awakening or tracheal extubation. CONCLUSIONS: CPB does not affect propofol requirements or immediate postoperative recovery compared with the off-pump technique.