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Chlorhexidine is a widely used skin antisepsis preparation and is an ingredient in toothpaste and mouthwash. It is an especially effective antiseptic when combined with alcohol. Its antimicrobial effects persist because it is binds strongly to proteins in the skin and mucosa, making it an effective antiseptic ingredient for handwashing, skin preparation for surgery and the placement of intravascular access. Catheters impregnated with chlorhexidine and antimicrobial agents can reduce the incidence of catheter-related bloodstream infections. Contact dermatitis related to chlorhexidine is not common in health care workers. The incidence of contact dermatitis to chlorhexidine in atopic patients is approximately 2.5 to 5.4%. Acute hypersensitivity reactions to chlorhexidine are often not recognised and therefore may be underreported. This review discusses the pharmacology, microbiology, clinical applications and adverse effects of chlorhexidine. [ABSTRACT FROM AUTHOR]

Newer generation drug-eluting stents are the most commonly inserted stent in the setting of percutaneous coronary intervention. This narrative review focuses on the evidence underpinning the perioperative management of patients with newer generation drug-eluting stents undergoing non-cardiac surgery. Six studies reported the incidence of major adverse cardiovascular events according to the time interval from percutaneous coronary intervention to non-cardiac surgery, and the comparative risks of newer and first generation drug-eluting stents. No study demonstrated an increased risk of major adverse cardiovascular events once three months had elapsed between stent implantation and non-cardiac surgery. Only one study included patients with third and fourth generation drug-eluting stents. Seven studies analysed the relationship between antiplatelet therapy, major adverse cardiovascular events and perioperative bleeding. The risks of major adverse cardiovascular events do not appear to be increased if antiplatelet therapy is ceased for less than seven days but are increased if it is discontinued for more than seven days. Most studies reported no differences in the incidence of major bleeding associated with antiplatelet therapy. The risk of perioperative major adverse cardiovascular events in non-cardiac surgery does not appear to be increased after three months following implantation with newer generation drug-eluting stents. However, the possibility of increased risk cannot be excluded as most studies were inadequately powered. The thrombotic risk is substantially reduced in patients with fourth (polymer free) generation drug-eluting stents, and urgent non-cardiac surgery can be considered one month after percutaneous coronary intervention. Larger multicentre studies are needed to define the optimal window for non-cardiac surgery after percutaneous coronary intervention and provide definitive perioperative strategies for patients presenting for non-cardiac surgery after the implantation of newer generation drug-eluting stents.

Strabismus correction surgery is the most common eye operation in children. Adults have approximately a 4% lifetime risk of developing strabismus. Current treatment options include pharmacological injection of botulinum toxin or bupivacaine, conventional corrective surgery, adjustable suture surgery and minimally invasive surgery. Repeated surgery is common as each operation has a 60%-80% chance of successful correction. The benefits of early surgical correction in large-angle strabismus in children outweigh the risks of anaesthesia. General anaesthesia is suitable for patients of all age groups, for complicated or repeated surgery, and bilateral eye procedures. Regional ophthalmic block reduces the incidence of oculocardiac reflex and emergence agitation, and provides postoperative analgesia, but requires a cooperative patient as many experience discomfort. Topical anaesthesia has been used in pharmacological injection, minimally invasive surgery, uncomplicated conventional strabismus surgery and some adjustable suture strabismus surgery. Its use, however, is only limited to cooperative adult patients. Prophylactic antiemesis with both ondansetron and dexamethasone is recommended, especially for children. A multimodal analgesia approach, including paracetamol, intravenous non-steroidal anti-inflammatory drugs, topical local anaesthetic and minimal opioid usage, is recommended for postoperative analgesia, while a supplementary regional ophthalmic block is at the discretion of the team.

This narrative review aims to describe the role of peripheral and central immune responses to tissue and nerve damage in animal models, and to discuss the use of immunomodulatory agents in clinical practice and their perioperative implications. Animal models of pain have demonstrated that nerve injury activates immune signalling pathways that drive aberrant sensory processes, resulting in neuropathic and chronic pain. This response involves the innate immune system. T lymphocytes are also recruited. Glial cells surrounding the damaged nerves release cytokines and proinflammatory mediators that activate resident immune cells and recruit circulatory immune cells. Toll-like receptors on the glial cells play a crucial role in the pathogenesis of chronic pain. Animal models indicate an immune mechanism of neuropathic pain. Analgesic drugs and anaesthetic agents have varied effects on the neuroimmune interface. Evidence of a neuroimmune interaction is mainly from animal studies. Human studies are required to evaluate the clinical implications of this neuroimmune interaction.

Clonidine has been used successfully to prolong the duration of action of local anaesthetics in peripheral nerve blocks, but its mechanism of action in this setting remains unclear. Some studies suggest that clonidine exerts a vasoconstrictor effect, limiting the washout of local anaesthetic from its site of deposition. We investigated this potential vasoconstrictor effect, using plasma ropivacaine concentrations as a surrogate measure of vasoconstriction, in patients who received transversus abdominis plane (TAP) blocks with and without clonidine. Eighty women undergoing laparoscopic gynaecological surgery were randomly assigned to receive one of four TAP block solutions: 0.2% ropivacaine (control), ropivacaine with clonidine 2 μg/kg (clonidine), ropivacaine with 1:400,000 adrenaline (adrenaline) or ropivacaine and a subcutaneous injection of clonidine 2 μg/kg (SC clonidine). The primary outcome was total venous plasma ropivacaine concentrations up to 6 h after the block. There were no significant differences in plasma ropivacaine concentrations between the control group and the clonidine group at any timepoint in the study, nor were there differences in either the mean maximum ropivacaine concentration ( C max ) (1.99 μg/mL versus 2.05 μg/mL, P = 0.712) or the time to maximum concentration ( T max ) (51.0 min versus 56.0 min, P = 0.537). The SC clonidine group also did not differ significantly from the controls ( C max 2.13 μg/mL versus 1.99 μg/mL, P = 0.424; T max 43.5 min versus 51.0 min, P = 0.201). Plasma ropivacaine concentrations in the adrenaline group were significantly lower than the controls from 10 to 90 min ( P < 0.003 for each comparison), and the C max was less than that of the control group (1.36 μg/mL versus 1.99 μg/mL, P < 0.001) with a longer T max (103.5 min versus 51.0 min, P = 0.001). These findings indicate that clonidine at a concentration of 1.35 μg/mL added to ropivacaine for TAP blocks did not produce a reduction in plasma ropivacaine concentrations. This suggests a lack of vasoconstrictor effect during TAP blocks. Further studies should evaluate whether vasoconstriction occurs when clonidine is used at higher concentrations or for other blocks.

The TEG® 5000 and novel TEG® 6s measure the viscoelasticity of whole blood during in vitro clot formation. The two devices measure similar coagulation variables but utilize distinctly different technologies. This study aimed to determine the correlation and agreement between the thrombelastographic parameters obtained by the two devices during liver transplant surgery. We obtained blood samples at six predefined intervals during the surgery of 10 consecutive patients. Two operators proficient in the use of the TEG® 6s and TEG® 5000 systems performed thrombelastographic measurements on each sample: non-citrated TEG® 5000, citrated TEG® 5000 and citrated TEG® 6s. Agreement and correlation were assessed using Bland Altman plots and Lin's concordance correlation. There was considerable inter-device variability for the different parameters measured by the TEG® 5000 and TEG® 6s devices. Acceptable agreement was observed when results were within the normal reference ranges. However, with increasing coagulopathy, agreement was poor and results could not be considered interchangeable. Although each of the three tests appeared reliable for qualitative detection of abnormalities of clot formation during liver transplant surgery, we found their quantitative results were not interchangeable.

This study evaluated the effects of haemodilution with either 6% hydroxyethyl starch (HES) 130/0.4 (Voluven(®)) or 0.9% normal saline (NS) on blood coagulation in vitro. Haemodilution with 6% HES 130/0.4 impaired coagulation, as indicated by the changes in thromboelastographic parameters k-time, α-angle and maximum amplitude. Light transmission aggregometry and multiple electrode aggregometry demonstrated that impaired platelet receptor function occurred only at high levels of haemodilution (40%) with both fluids, but there was no significant difference between the two fluids (P=0.05). The thromboelastographic functional fibrinogen assay showed that the fibrinogen component of clot strength was significantly impaired with haemodilution with HES 130/0.4 compared with haemodilution with NS (whole blood [14.4 ± 4.6 mm] versus 40% HES dilution [3.7 ± 1.9], [P=0.001]; versus 40% NS dilution [10.4 ± 4.6], [P=0.129]). These findings suggest that there is little difference between HES or NS in relation to coagulation or platelet function during minor or moderate haemodilution, but at high levels of haemodilution with HES, fibrinogen activity is more impaired compared with NS.

We investigated the in vitro viscoelastic changes of progressive haemodilution with 4% albumin compared with normal saline (NS) using rotational thromboelastometry (ROTEM(®), Pentapharm Co., Munich, Germany). Whole blood samples obtained from 20 healthy volunteers were diluted in vitro with 4% albumin or NS by 10%, 20% and 40%. Fibrinogen concentration and ROTEM(®) (EXTEM [screening test for the extrinsic haemostasis system], FIBTEM [EXTEM-based assay for the fibrin part of the clot]) variables including coagulation time, clot formation time (CFT), α-angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each degree of haemodilution. There was no significant difference in fibrinogen concentration at equivalent haemodilutions with normal saline and 4% albumin solutions. Forty percent haemodilution with albumin significantly prolonged coagulation time (EXTEM P=0.007, FIBTEM P=0.0001) and significantly decreased lysis index (FIBTEM P=0.009) compared with NS. A significant decrease in maximum clot firmness from undiluted measurements (P=0.05) was observed at lower haemodilutions with albumin (20% with EXTEM, 10% with FIBTEM) compared with NS (40% with EXTEM and FIBTEM). The adverse effects of large degrees of haemodilution with 4% albumin solution are in excess of what can be explained by haemodilution alone. This study suggests that large degrees of haemodilution with albumin impair fibrinogen activity to a greater extent than equivalent degrees of haemodilution with NS.

Objective: To describe the technique of isolated limb infusion (ILI) for regional high dose chemotherapy in patients with advanced malignancies confined to a limb, as currently practiced at Melanoma Institute Australia (MIA)., Background: ILI is progressively being used around the world but to date the reported response rates are generally lower than those reported by MIA., Discussion: This description of the ILI protocol at MIA provides details that may allow other surgeons to improve results., (© 2013 Wiley Periodicals, Inc.)

Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A number of centers around the world have reported their results using this procedure. In this study a systematic review of reported ILI experiences was undertaken. A literature search was conducted according to the guidelines for systematic reviews in order to select eligible papers reporting limb toxicity and response rates following ILI using melphalan and actinomycin D to treat limb melanoma. A total of 576 patients from seven publications were included. Regional toxicity following ILI was low: no visible effect of the treatment or slight erythema or edema was observed in 79% of the patients, while considerable erythema and/or edema with blistering was experienced by 19%. In 2% there was a threatened or actual compartment syndrome. No procedure-related amputation was reported. Complete response occurred in 33% of the patients and partial response in 40%, an overall response rate of 73%. Stable disease and progressive disease were achieved in 14% and 13% of the patients, respectively. This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low, with satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response., (© 2014 Wiley Periodicals, Inc.)

Perioperative cardiac complications are a common cause of death and major morbidity in patients undergoing non-cardiac surgery. Preoperative evaluation and medical optimisation can improve outcomes, although the evidence base is limited. Evidence of effectiveness is strongest for prophylactic use of β-blockers in high-risk patients and aspirin in patients with coronary artery disease. Particular challenges arise among patients with heart failure or valvular heart disease or those receiving antithrombotic therapy for coronary artery stents or atrial fibrillation. Close liaison between general practitioners, surgeons, anaesthetists and cardiologists is needed for optimising preoperative management and subsequent clinical outcomes in high-risk patients.

Interventional neuroradiology is a rapidly expanding field, and the complexity and duration of these procedures makes anaesthetic support essential to their success. Such has been the development in this area, that the American Heart Association has published a scientific statement on the indications for these procedures. A detailed understanding of patient pathology, the technical aspects of the interventions and their associated risks, and the remote location in which they are performed are important for providing expert anaesthetic care. The aim of this article is to provide a description and contemporary analysis of the common interventional neuroradiology procedures relevant to the anaesthetist. This article will cover the management of intracranial aneurysms, cerebral vasospasm following intracranial haemorrhage, intracranial and spinal arteriovenous malformations, idiopathic intracranial hypertension, carotid artery stenting, intra-arterial thrombolysis for stroke and endovascular treatment of intracranial atherosclerosis. Protection from ionising radiation and acute kidney injury are also discussed.

Background: Isolated limb infusion (ILI), introduced in 1992, is a technique used to deliver regional chemotherapy to treat advanced melanoma confined to a limb. Adjusting melphalan dose according to ideal body weight (IBW) has been proposed as a method of decreasing limb toxicity without compromising outcome. The current study analyzed this proposed dose adjustment., Methods: We reviewed 99 consecutive patients with lower extremity melanomas treated by ILI at our institution between May 1998 and February 2009. Toxicity and outcomes were tested for correlation with differences between administered dose and calculated adjusted dose, both in mg and mg/L, and with differences between actual limb volume and calculated adjusted limb volume., Results: The median actual body weight was 71 kg, whereas the calculated median IBW was 57 kg (p < .001). Median administered melphalan dose was 7.7 mg/L. The median calculated adjusted dose was 6.5 mg/L (range 3.2-9.3 mg/L, p < .001). None of the three aforementioned parameters correlated with either Wieberdink toxicity grade or outcome. BMI did not correlate with toxicity either. Interestingly, a higher total melphalan dose did not only correlate with higher toxicity, but also with a lower response rate., Conclusions: Adjusting the melphalan dose for IBW does not appear to reduce toxicity following ILI for melanoma. The effect on outcome remains uncertain. More research is needed to optimize melphalan concentrations in individual patients during ILI to limit toxicity without compromising the response.

Background: Isolated limb infusion (ILI) with cytotoxic drugs has been used since 1992 to treat advanced melanoma confined to a limb. Over this time the technique has undergone progressive modification. In this study we evaluated our experience with ILI by analyzing outcome and toxicity from an "early" and a "late" treatment period., Methods: We compared the results from our institution for 94 patients treated by ILI in the early period (1992-1999) with the results for 91 patients treated in the late period (2000-2007). All patients had advanced limb melanoma and received a combination of melphalan and actinomycin D., Results: The patient characteristics of the early and late groups were similar, but there was greater tumor load in the late group, who had a significantly greater number of lesions (median 4 vs. 5; p = 0.02) and deeper tumor infiltration (p = 0.03). Drug circulation times were longer in the late group: 22 vs. 31 min (p < 0.0001). In the late group, higher initial and final limb temperatures were achieved. Overall response rates were 85% in both groups. The late treatment group showed a trend towards less toxicity (p = 0.06)., Conclusions: Response rates and survival following ILI for advanced melanoma in our late treatment period were similar to those of our early treatment period, despite the significantly greater tumor load of the patients treated in the late period. This could be attributed to increased experience and protocol modifications, which allowed longer drug exposure times and higher limb temperatures to be achieved without increased toxicity.

Importance of the Field: Isolated limb infusion (ILI) is a simple, minimally invasive technique of delivering high concentrations of cytotoxic drugs to a diseased limb for achieving disease control in that limb. Recent studies have suggested that mild hyperthermic (38 degrees C) ILI might be the best initial treatment for extensively recurrent limb melanoma given its simplicity, low morbidity and a complete response rate of 30 - 40%., Areas Covered in This Review: Since 1994 when ILI was first described by Thompson et al., the procedure has been adopted by several centres around the world; research and improvements in the technique have resulted in reduction in limb toxicity without reducing its clinical efficacy. The pharmacokinetics of melphalan and the clinical efficacy and adverse effects of ILI from various centres are summarised. Minor but possibly important differences in the ILI techniques used in different institutions may be important in improving its efficacy and reducing the toxic effects., What the Reader Will Gain: An understanding of the efficacy and toxicity associated with ILI with cytotoxic drugs in melanoma patients and of methods to optimise regional therapy for malignant disease in a limb., Take Home Message: ILI with mild hyperthermia (38 degrees C) is well tolerated with tumour remission rates in melanoma patients similar to those achieved by isolated limb perfusion. Mild (grade I - II) and moderate/severe (grade > or = III) limb toxicities occur in 58 - 68% and 32 - 41% of patients, respectively, but long-term morbidity is rare. A high peak and high final melphalan concentration in the infusate, the AUC of melphalan concentration in the infusate and an increased postoperative serum creatine phosphokinase concentration are factors predictive of acute regional toxicity. Drug dose adjusted for ideal body weight and gender may reduce acute toxicity following ILI. It has been suggested that the use of papaverine prior to the infusion of melphalan might increase its efficacy, but it may also increase toxicity. Large prospective studies are needed to more accurately define the perioperative factors that influence acute regional toxicity after ILI and to establish strategies to optimise clinical outcome.

Introduction: Isolated limb infusion (ILI) is an effective, minimally invasive treatment option that delivers high-dose regional chemotherapy to treat metastatic melanoma confined to a limb. In some patients, however, locoregional disease does not respond to the treatment or extensive recurrence occurs so that an amputation may become inevitable. In this study we analyzed indications for and results of amputation in these cases., Methods: 14 patients were identified in whom amputation of the affected limb had to be carried out after failure of ILI., Results: Following ILI, three patients had a complete response, seven had a partial response, two had stable disease and two patients had progressive disease. The median duration of response after ILI was 7 months (range 2-30). The median interval between ILI and amputation was 10 months. Amputation was performed in six of 20 patients who had been treated with an upper limb ILI, compared to eight amputations that were performed in 215 patients who had been treated with a lower limb ILI (P = .001). The indications for amputation were severe pain due to progression of tumor (n = 3), uncontrollable and troublesome tumor progression (n = 6) and bleeding from ulcerated lesions (n = 5). Five patients developed stump recurrence after amputation; these were treated by excision or radiation. Six of the eight patients who had a lower limb amputation became ambulant with the aid of prosthesis. Median survival after amputation was 13 months: three patients survived more than 5 years., Conclusions: Amputation following upper extremity ILI is more common compared to lower extremity ILI. Amputation may provide effective long-term palliation in selected patients when there is extensive inoperable progressive or recurrent disease after ILI.

Introduction: The treatment of elderly patients with advanced metastatic melanoma confined to a limb remains controversial. Isolated limb infusion (ILI) is an effective minimally invasive alternative to isolated limb perfusion (ILP) and is therefore a potentially valuable therapeutic option for this group., Methods: From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin-D was used., Results: Eighty-six patients (46%) were >or=75 years of age (range: 75-93). The patient characteristics in both groups were comparable except that the older group comprised more women (71% vs. 54%; P = 0.02) and had a lower body mass index (median: 24.4 vs. 26.4; P = 0.008). Complete response rates were 34% for those >or=75 years and 41% in the younger group (P = 0.28). There was no difference in limb recurrence free interval after a complete response (median: 24 months for both groups; P = 0.51) or in survival (median: 36 months for <75, 39 months for >or=75; P = 0.36) between both groups. Older patients experienced less limb toxicity after the procedure (Wieberdink grade III/IV toxicity in 36%) compared with younger patients (51%; P = 0.009) while systemic toxicity, complications, and long-term morbidity were similar., Conclusions: Elderly patients with advanced metastatic melanoma of the limb experience the same or lower toxicity after ILI compared with younger patients while response rates, limb recurrence free interval, survival, and morbidity are similar. ILI is an attractive alternative to the more laborious ILP, especially for older patients.

Introduction: Isolated limb infusion (ILI) with cytotoxic drugs is a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb. Response rates and duration of response following ILI are similar to those after ILP. Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome. In this study we sought to determine factors predicting toxicity following ILI., Methods: From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin D was used. Drug circulation time was 20-30 min under mild hyperthermic conditions (38-39 degrees C). Limb toxicity was assessed using the Wieberdink scale., Results: The average patient age was 74 years (range 29-93 years) and 62% were female. Most patients (134/185) had MD Anderson stage III disease (satellites and in-transit metastases). Toxicity grade I (no reaction) occurred in 3 patients, grade II (slight erythema and edema) in 105 patients, grade III (considerable erythema and edema +/- blistering) in 72 patients, and grade IV (threatened or actual compartment syndrome) in 5 patients. No patient developed grade V toxicity (requiring amputation). On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration. Surprisingly, a greater rise in the CO(2) level during the procedure was associated with lower toxicity in the univariate analysis. Increased serum creatine phosphokinase (CK) postoperatively was related to higher toxicity score. In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity., Conclusions: ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb. Regional acute toxicity following ILI is mild to moderate in most patients. Based on the predictive factors found in this series, altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness.

Ankylosing spondylitis can present significant challenges to the anaesthetist as a consequence of the potential difficult airway, cardiovascular and respiratory complications, and the medications used to reduce pain and control the disease. There is also an increased risk of neurological complications in the peri-operative period. Awake fibreoptic intubation is the safest option in those patients with a potentially difficult airway as it allows continuous neurological monitoring while achieving a definitive airway. Neurophysiological monitoring (somatosensory and motor evoked potentials) should be considered in patients undergoing surgery for cervical spine deformity. The medical management of the disease has improved with the use of anti-tumour necrosis factor-alpha agents. There is potential for increased wound infection in patients taking these drugs. This article reviews the anaesthetic issues in patients with ankylosing spondylitis. The challenge to the anaesthetist is in the understanding of these issues so that appropriate management can be planned and undertaken.

Introduction: In the treatment of patients with advanced limb melanoma a major treatment dilemma can arise when distant metastases are present also. Isolated limb infusion (ILI) has proved to be a useful limb-saving treatment and could potentially be of palliative value in patients with American Joint Committee on Cancer (AJCC) stage IV melanoma., Methods: We identified 37 patients with advanced symptomatic limb disease as well as documented distant metastases at the time of their ILI. In all patients a drug combination of melphalan and actinomycin D was used., Results: Fifty one percent had visceral distant metastases and 49% had cutaneous distant metastases only. The overall response rate in the treated limb was 76% [complete response (CR) rate 22%, partial response (PR) rate 54%]. Median response duration was 11 months (28 months for patients with CR; p = 0.08). Median survival after CR was 22 months, 17 months after PR, and only 4 months for those with stable or progressive disease (p = 0.002). Patients with visceral distant metastases had a significantly decreased survival compared with those with cutaneous distant metastases only (8 and 21 months, respectively; p = 0.03). Limb salvage was achieved in 86% of the patients. The procedure was well tolerated, with only one patient developing Wieberdink grade IV toxicity (threatened/actual compartment syndrome) and none requiring amputation as a result of the procedure (grade V toxicity)., Conclusions: Minimally invasive ILI can effectively be used as palliative treatment to provide local tumor control and limb salvage in stage IV melanoma patients with advanced, symptomatic limb disease.

Background: Isolated limb infusion (ILI) is a minimally invasive technique for delivering regional chemotherapy in patients with advanced and metastatic melanoma confined to a limb. It is essentially a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation., Methods: From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1993 and 2007 were identified. In all patients a cytotoxic drug combination of melphalan and actinomycin-D was used. Drug circulation time was 20-30 min under mild hyperthermic conditions (38-39 degrees C)., Results: The majority of patients (62%) were female. Their average age was 74 years (range 29-93 years). Most patients had MD Anderson stage III disease (134/185). The overall response rate was 84% [complete response (CR) rate 38%, partial response rate 46%]. Median response duration was 13 months (22 months for patients with CR; P = 0.01). Median follow-up was 20 months and median survival was 38 months. In those patients with a CR, the median survival was 53 months (P = 0.005). CR rate and survival time decreased with increasing stage of disease. On multivariate analysis significant factors for a favorable outcome were achievement of CR, stage of disease, thickness of primary melanoma, the CO(2 )level in the isolated circuit, and a Wieberdink limb toxicity score of III (considerable erythema and edema)., Conclusion: The response rates and duration of response after ILI are comparable to those achieved by conventional ILP. ILI is a minimally invasive alternative to the much more complex and morbid conventional ILP technique for patients with advanced metastatic melanoma confined to a limb.

Background: Isolated limb infusion (ILI) is a minimally invasive technique for delivering high-dose regional chemotherapy. We report our experience with ILI for the treatment of soft tissue sarcoma (STS)., Methods: From our prospective database, 21 patients with STS of the limb treated with ILI between 1994 and 2007 were identified. In all patients, a high-dose cytotoxic drug combination was used., Results: There were 14 men, and the median age was 60 years (range, 18-85 years). Eighteen patients (86%) had lower limb tumors. All patients had advanced local disease. The procedure was well tolerated. Fourteen patients (67%) received ILI before definitive surgery. The overall response rate was 90% (complete response [CR] rate 57%, partial response rate 33%). The disease-specific overall survival was 61.9% (median follow-up, 28 months). Only American Joint Committee on Cancer stage was associated with overall survival. The local recurrence rate was 42%. CR and malignant fibrous histiocytoma tumor subtype were associated with a lower local recurrence rate. A lower initial skin temperature (median 35.8 degrees C) was associated with a CR (P = .033). Patients who had a steep increase in intramuscular temperature during the procedure were more likely to have a CR (P = .055). Classification tree analysis identified patients with an initial PaO(2) of >/=194 mmHg as being more likely to have a CR. Ultimately, the overall limb salvage rate was 76%., Conclusion: The outcomes after ILI are comparable to those achieved by conventional isolated limb perfusion. ILI is a minimally invasive alternative to isolated limb perfusion for patients with advanced STS of the extremity.

Isolated limb infusion (ILI) provides a simple, minimally invasive, and yet effective method of delivering high doses of cytotoxic drugs into tumor tissue with minimal systemic side effects because there is no significant drug leakage into the systemic circulation. The ILI technique is a technically less complex procedure than conventional ILP that can be used in patients who have advanced or persistently recurrent disease in an extremity. It is an attractive palliative option because it preserves limb function and maintains quality of life. Repeat ILI is safe and effective. Because the risk for systemic leakage is extremely low, ILI provides an excellent model in which to test new drugs and drug combinations.

The use of intravascular iodinated contrast media (ICM) in radiological investigations is common. Increasingly, anaesthetists and intensivists are involved in the care of patients undergoing these investigations. Whilst the use of ICM is generally safe there are important adverse effects that need to be recognised and measures instigated to prevent or treat these effects. In patients at risk of developing adverse reactions it is important to consider alternative modes of imaging so that ICM can be avoided. Strategies for the prevention of ICM nephropathy should be considered in all patients receiving ICM. Currently intravascular volume expansion with 0.9% saline has the strongest evidence base. The use of isotonic sodium bicarbonate combined with N-acetylcysteine appears promising in providing further benefits. Although the use of N-acetylcysteine alone has not been shown to significantly reduce the incidence of ICM nephropathy it is cheap, has few adverse effects and it would seem reasonable to continue its use in conjunction with intravascular volume expansion. The routine use of corticosteroid and antihistamine premedication is not always effective in preventing general adverse reactions.

Purpose of Review: New insights into the role of platelets in haemostasis have enabled a better understanding of the pathophysiology of conditions associated with thrombocytopenia. The development of new drugs and the advances in blood transfusion technology have improved the clinical management of patients with thrombocytopenia. The aim of this article is to provide a concise review of major advances in the perioperative management of patients with thrombocytopenia., Recent Findings: Thrombocytopenia is a symptom, and the underlying cause must be evaluated. Immunotherapy, corticosteroids, immunosuppressive drugs and thrombopoietic growth factors can increase the number of platelets in thrombocytopenic patients. Further, a better understanding of the pathophysiology of heparin-induced thrombocytopenia type II and the development of direct thrombin inhibitors have improved the management of these patients, especially in the perioperative period., Summary: The lack of clinical methods for predicting which type of patients with thrombocytopenia are at risk of bleeding and the effectiveness of various platelet preparations call for research initiatives to provide better guidelines for transfusion practice. Controlled clinical trials are required to evaluate strategies for the prophylactic use of platelets and thrombopoietic factors in idiopathic thrombocytopenic purpura and the use of direct thrombin inhibitors in patients with heparin-induced thrombocytopenia.

Purpose: Recurrent disease confined to a limb is a frequently encountered clinical problem in patients with melanoma. Regional chemotherapy by isolated limb perfusion (ILP) provides effective treatment but is invasive, complex and costly. Isolated limb infusion (ILI) is a simple yet effective alternative to ILP., Materials and Methods: ILI involves drug administration into a limb via percutaneously inserted catheters after vascular isolation of the limb has been achieved with a tourniquet. The infused drug is circulated for 30 minutes via a simple extracorporeal circuit incorporating a heater (to produce mild hyperthermia)., Results: Limb tumour remission rates are similar to those achieved by conventional ILP. ILI is well tolerated, and elderly patients and those with major medical co-morbidities and serious peripheral vascular problems can be treated., Conclusions: ILI with mild hyperthermia is an established alternative to hyperthermic ILP for patients with recurrent limb melanoma. It can also be used for patients with soft tissue sarcomas and a variety of serious, chronic dermatological conditions.

The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver. There is an association between PRIS and propofol infusions at doses higher than 4 mg.kg(-1).h(-1) for greater than 48 h duration. Sixty-one patients with PRIS have been recorded in the literature, with deaths in 20 paediatric and 18 adult patients. Seven of these patients (four paediatric and three adult patients) developed PRIS during anaesthesia. It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram. Predisposing factors include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. Treatment options are limited. Haemodialysis or haemoperfusion with cardiorespiratory support has been the most successful treatment.

Botulinum toxin is used as first line therapy for some muscular disorders, and is efficacious in treating hypersecretory and some pain syndromes. When used appropriately it has a good safety profile. It has been evaluated in treating a number of conditions that as yet do not have obvious effective or beneficial treatment. With the greater acceptance and use of botulinum toxin therapy for cosmetic purposes, botulinum toxin use will increase. An understanding of the pharmacology, and potential adverse effects is essential for the physician when managing patients having or who would benefit from botulinum toxin therapy.

Purpose: To review the long-term duration of limb tumor complete remission (CR) and patient survival following therapeutic hyperthermic isolated limb perfusion (ILP) with cytotoxic drugs for melanoma., Methods: A retrospective case series of 124 ILPs performed in 111 patients., Results: There were 120 assessable ILPs. Patient staging (M.D. Anderson system) was stage II 11.7%, stage IIIA 44.2%, stage IIIAB 33.3%, and stage IV 10.8%. CR was initially attained after 83 ILPs (69.2%) and partial remission (PR) after 19 ILPs (15.8%). Limb CR was maintained in 28 (33.7%) of the 83 cases. Disease recurred in the perfused limb after an initial CR in the remaining 55 cases (median time to recurrence, 11 months); in 19 of these cases, the limb was disease-free at last follow-up after further locoregional treatment. A long-term CR was achieved, with or without further treatment, in 47 (56.6%) of the 83 cases in which an initial CR had occurred (mean follow-up, 97 months; median, 65 months). There was no significant difference in long-term local remission for stage IIIA and IIIAB patients. Five-year survival for those who had a partial or no response to ILP was 7%. Ten-year survival for those who had a long-term CR was 49%., Conclusions: ILP, with or without further locoregional treatment, achieved long-term control of recurrent and metastatic limb disease in 56.6% of cases in which an initial CR was achieved. A complete response to ILP was a positive prognostic indicator for survival, probably reflecting more favorable tumor biology in this subset of patients.

Aims: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma., Methods: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery., Results: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival., Conclusions: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.

Background: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used to treat pseudomyxoma peritonei. The aim of this prospective study was to evaluate survival outcome and treatment-related prognostic markers in patients who underwent CRS and PIC for pseudomyxoma peritonei from appendiceal mucinous neoplasms., Methods: Survival data and 12 clinicopathological and treatment-related prognostic variables for survival were obtained prospectively in 50 consecutive patients (23 men). Univariate analysis was used to determine their prognostic significance for overall survival, determined from the time of CRS., Results: The mean(s.d.) age was 52(12) years. Eighteen patients had moderate complications, and six patients had severe complications that required operation or intensive care support. Two patients died after surgery. The actuarial 5-year survival rate was 69 per cent. Univariate analysis demonstrated that the extent of previous surgery (P = 0.045) and Ronnett's histopathological classification (P < 0.001) were significantly related to overall survival., Conclusion: CRS combined with PIC was associated with improved survival in patients with less extensive previous surgery and diffuse peritoneal adenomucinosis histopathological type.

Transfusion-related acute lung injury (TRALI) is a serious and potentially fatal complication of transfusion of blood and blood components. TRALI is under-diagnosed and under-reported because of a lack of awareness. A number of models have been proposed to explain the pathogenesis of TRALI: an antibody mediated model; a two-event biologically active mediator model; and a combined model. TRALI can occur with any type of blood product and can occur with as little as one unit. Its presentation is similar to other forms of acute lung injury and management is predominantly supportive. The main strategy in combating TRALI is prevention both through manipulation of the donor pool and through clinical strategies directed at reducing transfusion of blood products including, but not limited to, evidence-based lower transfusion thresholds. This article presents a review of TRALI and addresses the definition, pathology, pathogenesis, clinical manifestations, treatment and prevention of the syndrome.

Background: Primary or secondary tumors of kidney often are managed by partial nephrectomy. Intraoperative blood loss can be significant. Laparoscopic partial nephrectomy may be even more challenging. We developed the Inline radiofrequency coagulation (ILRFA) probe for liver surgery. It uses radiofrequency energy to make a linear coagulative plane and considerably reduces bleeding during parenchymal transection. In this stud,y we tested the efficiency of ILRFA in ovine kidney., Method: Seven sheep were used in this study. Under general anesthetic, a laparotomy was performed in each sheep. The first two sheep were used as pilot experiments. Five partial nephrectomies were made in the remaining five sheep using ILRFA. As a control, a matching partial nephrectomy was made in each sheep using diathermy and sutures. Blood loss was measured by determining the difference in the weights of dry sponges and blood stained sponges after resection. A paired t test was used to compare the bleeding between the control and the ILRFA technique., Results: The mean blood loss using ILRFA was 33.14 g (SD 17) and 123.43 g (SD 72) in the control group. The bleeding was significantly reduced in the ILRFA group, with a P value of 0.0056. The time taken for applying the ILRFA was 3-4 min., Conclusion: We have achieved partial nephrectomy in ovine kidney using radiofrequency energy with significantly reduced blood loss.

Background: This study aims to assess the survival of patients who underwent peritonectomy, to assess the morbidity and mortality associated with the procedure and to review the published reports on the survival of patients with peritoneal spread of colorectal cancer (CRC)., Methods: Peritonectomy involves resection of all visible peritoneal tumour and is followed by heated intraperitoneal chemotherapy. Peritonectomy with heated intraperitoneal chemotherapy is associated with a 3-year survival of 30-50% in patients with low peritoneal cancer index (PCI) with peritoneal carcinomatosis from CRC. There are approximately 1000 patients in phase 2 studies and a large survival advantage was shown in a randomized control trial. We have carried out over 100 peritonectomy procedures. This study describes 22 patients with peritoneal spread of gastrointestinal cancer treated with peritonectomy between 1996 and March 2005. Twenty of these patients had primary colorectal cancer and two patients had primary small bowel cancer., Results: Of the 22 patients who underwent peritonectomy, 8 patients are now deceased. The median follow up is now 16.1 months. At 12 months, the survival was 61.5% and at 24 months the survival was 46.1%, which are creditable results comparable with the world published reports. We found that those patients with all macroscopic residual tumour removed at the end of the procedure (completeness of cancer resection, CCR O) had improved 24-month survival compared with patients in whom there was incomplete tumour resection (53.3% survival vs 22.2%, respectively, P = 0.024). Patients with a PCI score less than 13 had better survival (P = 0.0003)., Conclusions: Peritonectomy for peritoneal carcinomatosis from CRC offers patients improved survival. Our results are consistent with the published data with respect to improved survival in patients with low PCI and complete cytoreduction.

Obesity is becoming a major public health problem throughout the world. It is now the second leading cause of death in the United States and is associated with significant, potentially life-threatening co-morbidities. Significant advances in the understanding of the physiology of body weight regulation and the pathogenesis of obesity have been achieved. A better understanding of the physiology of appetite control has enabled advances in the medical and surgical treatment of obesity. Visceral or abdominal obesity is associated with an increased risk of cardiovascular disease and type 2 diabetes. Various drugs are used in the treatment of mild obesity but they are associated with adverse effects. Surgery has become an essential part of the treatment of morbid obesity, notwithstanding the potential adverse events that accompany it. An appreciation of these problems is essential to the anaesthetist and intensivist involved in the management of this group of patients.