Entonox® inhalation to reduce pain in common diagnostic and therapeutic outpatient urological procedures: a review of the evidence.

INTRODUCTION: Entonox(®) (50% nitrous oxide and 50% oxygen; BOC Healthcare, Manchester, UK) is an analgesic and anxiolytic agent that is used to successfully reduce pain and anxiety during dental, paediatric and emergency department procedures. In this article we review the application and efficacy of Entonox(®) in painful local anaesthesia urological procedures by performing a systematic review of the literature. METHODS: A MEDLINE(®) search was performed using the terms 'nitrous oxide', 'Entonox', 'prostate biopsy', 'flexible cystoscopy' and 'extracorporeal shock wave lithotripsy'. English language publications of randomised studies were identified and reviewed. RESULTS: The search yielded five randomised studies that investigated the clinical efficacy of Entonox(®) as an analgesic for day case urological procedures. Three randomised controlled trials (RCTs) investigated Entonox(®) in transrectal ultrasonography guided prostate biopsy. All three reported significant reductions in pain score in the Entonox(®) versus control groups. One RCT reported significant reduction in pain during male flexible cystoscopy in the Entonox(®) group compared with the control group. One RCT, which examined the use of Entonox(®) during extracorporeal shock wave lithotripsy, found its use significantly decreased the pain score compared with the control group and this was comparable to intravenous pethidine. CONCLUSIONS: Evidence from varied adult and paediatric procedures has shown Entonox(®) to be an effective, safe and patient acceptable form of analgesia. All published studies of its use in urological day case procedures have found it to significantly reduce procedural pain. There is huge potential to use this cheap, safe, effective analgesic in our current practice.

Prevention and treatment of urinary tract infection with probiotics: Review and research perspective.

The spiralling costs of antibiotic therapy, the appearance of multiresistant bacteria and more importantly for patients and clinicians, unsatisfactory therapeutic options in recurrent urinary tract infection (RUTI) calls for alternative and advanced medical solutions. So far no sufficient means to successfully prevent painful and disabling RUTI has been found. Even though long-term oral antibiotic treatment has been used with some success as a therapeutic option, this is no longer secure due to the development of bacterial resistance. One promising alternative is the use of live microorganisms (probiotics) to prevent and treat recurrent complicated and uncomplicated urinary tract infection (UTI).The human normal bacterial flora is increasingly recognised as an important defence to infection. Since the advent of antibiotic treatment five decades ago, a linear relation between antibiotic use and reduction in pathogenic bacteria has become established as medical conventional wisdom. But with the use of antibiotics the beneficial bacterial flora hosted by the human body is destroyed and pathogenic bacteria are selectively enabled to overgrow internal and external surfaces. The benign bacterial flora is crucial for body function and oervgrowth with pathogenic microorganisms leads to illness. Thus the concept of supporting the human body's normal flora with live microorganisms conferring a beneficial health effect is an important medical strategy.

Nitrous oxide inhalation to improve patient acceptance and reduce procedure related pain of flexible cystoscopy for men younger than 55 years.

PURPOSE: Flexible cystoscopy in men younger than 55 years is painful despite the current best standard anesthesia (20 ml 2% lidocaine gel 15 minutes before endoscopy). The anesthetic value of lidocaine gel is debated and led us to seek an alternative. Nitrous oxide is a well established analgesic and anxiolytic agent, and it significantly reduces pain associated with transrectal ultrasound guided prostate biopsy. We studied its use in flexible cystoscopy in men younger than 55 years. MATERIALS AND METHODS: A total of 61 patients were prospectively randomized to receive air (31) or Entonox (30). Both groups had 3 minutes of gas via a breath activated facemask (either Entonox or air) before endoscopy. The gel control group was comprised of 8 patients who underwent cystoscopy after instillation of lidocaine gel. The air and Entonox groups had lidocaine gel as per best standard. Vital signs were recorded before, during and after cystoscopy. Patients completed a visual analog score for gel insertion and cystoscopy. RESULTS: There were no statistically significant differences between the groups in terms of baseline characteristics. Pain scores for cystoscopy (p<0.001) and intraoperative pulse rate (p=0.008) were significantly less with Entonox. Side effects were transient and seen more often with Entonox (p<0.05). More of the air group would require more analgesia (p=0.001) or a general anesthetic (p=0.011) if undergoing repeat cystoscopy. CONCLUSIONS: Nitrous oxide inhalation significantly reduces cystoscopy related pain without significant complications. We propose that Entonox should be the anesthetic agent of choice for men younger than 55 years.

Urethral catheter: a pain in the neck!

Long-term urinary catheterization is well recognized in the literature as being associated with significant morbidity and mortality. We present a rare and previously unreported complication of a cervical spine abscess resulting from methicillin-resistant Staphylococcus aureus septicaemia originating from the urinary tract in a patient with a urinary catheter.

Nitrous oxide (Entonox) inhalation and tolerance of transrectal ultrasound guided prostate biopsy: a double-blind randomized controlled study.

PURPOSE: We performed a randomized, placebo controlled double-blind trial to evaluate the effectiveness of Entonox (BOC Gases, Manchester, United Kingdom), that is 50% nitrous oxide and oxygen, as analgesia during transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: Patients referred for transrectal ultrasound guided prostate biopsy for the first time as an outpatient procedure were recruited subject to exclusion criteria and randomized to breathe Entonox or air via similar breath activated devices. At the end of the procedure patients completed a visual pain analog scale. Patients who refused study participation also completed the visual analog pain scale to assess the placebo effect of receiving gas through a mask. RESULTS: A total of 110 patients were studied. Statistical analysis using 1-way analysis of variance showed a highly significant difference in pain perception among the 3 groups (F [2,107] = 73.348, p <0.001). This significant decrease in pain was noted in the Entonox versus air and Entonox versus placebo groups. There was no significant difference in the air and placebo groups. Seven of the 51 patients receiving Entonox complained of feeling drowsy during the procedure, which resolved at completion of the procedure. In this group 49 patients would undergo this procedure again if needed. In 2 of the 45 patients in the group receiving air the procedure was abandoned due to pain, while another 19 would prefer more analgesia and 2 would prefer general anesthesia if the procedure was to be repeated. CONCLUSIONS: Our study shows that Entonox is a safe, rapidly acting and effective form of analgesia for the pain of prostate biopsy. We believe that it should be the analgesia of choice for this procedure.

Renal cell carcinoma: incidental detection during routine ultrasonography in men presenting with lower urinary tract symptoms.

OBJECTIVE: To compare renal cell carcinomas (RCCs) presenting incidentally in patients referred for lower urinary tract symptoms (LtJTS) with those presenting symptomatically, by stage, intervention and outcome. PATIENTS AND METHODS: The case notes of all male patients (100) diagnosed with RCC between 1991 and 1998 were reviewed and modes of presentation recorded. The patients were divided into two groups: those who were referred with LUTS (frequency, urgency, hesitancy, poor stream, nocturia) and in whom RCC would not have been suspected and was thus detected incidentally on routine ultrasonography; and all patients in whom carcinoma might have been suspected from their symptoms but, for the purposes of this study, also included patients in whom RCC was diagnosed during ultrasonography for unrelated intra-abdominal pathology. Details of diagnostic imaging and clinical staging were similarly recorded for both groups and where surgical intervention was undertaken, histopathological data were also noted. The clinical course and long-term outcome of incidentally detected tumours was then compared with their symptomatically presenting counterparts. RESULTS: The mean (range) follow-up for all patients was 30 (1.5-96) months; for those in the incidental group it was 31 (1-86) months and in the symptomatic patients 29 (1-96) months. Organ-confined disease was found in two-thirds of patients with incidental tumours and in 38% of those in whom the tumour may have been suspected; the difference was statistically significant (chi-squared test P<0.05). The mean (SD) size of tumours discovered incidentally and in symptomatic patients was 5.9 (1.94) cm and 9.2 (3.39) cm, respectively; this difference was also statistically significant (t-test, P<0.001). Of the 24 patients with incidentally detected tumours, 14 (58%) were alive with no recurrence, and of the 76 presenting symptomatically, 27 (35%) were alive with no recurrence at the last follow-up; disease survival curves showed a statistically better survival rate for those with organ-confined tumours. CONCLUSION: Incidentally diagnosed RCC represents a significant proportion of those who are ultimately diagnosed with the malignancy. Opportunities which arise for appropriate screening of the upper tracts during routine urological investigations (e.g. ultrasonography of the upper tracts in patients referred for LUTS) should be endorsed, contrasting with the more traditional approach, which argues that it yields no ultimate survival advantage.

Effect of a flooding dose of leucine in stimulating incorporation of constantly infused valine into albumin.

Recently, we demonstrated increased incorporation of [13C]valine tracer into muscle protein after administration of a flooding dose of L-leucine. We have now investigated the possibility of a similar effect on albumin synthesis in the same group of volunteers. We gave L-[1-13C]leucine (20 atom%, 0.05 g/kg) during the final 90 min of a 7.5-h primed constant infusion of L-[1-13C]valine (99 atom%, 1.5 mg/kg prime constant infusion of 1.5 mg.kg-1.h-1) in healthy male volunteers in the postabsorptive state. Blood samples, taken at 0.5- to 1-h intervals during the constant infusion and at 5- to 30-min intervals during the application of the flooding dose, were analyzed for the concentration and 13C enrichment of leucine, valine, and their ketoacids. Albumin was isolated and hydrolyzed, and the enrichments of incorporated valine and leucine were compared with the mean enrichment of various possible precursor pools to calculate the apparent rate of albumin protein synthesis according to the standard procedures. During constant infusion of [13C]valine tracer the rate of albumin synthesis (measured using alpha-ketoisovalerate labeling as a surrogate for the true precursor) was 0.250 +/- 0.041%h (SD), a value identical to that routinely obtained using constant leucine tracer infusion and alpha-ketoisocaproate labeling. During the application of the flooding dose of leucine, the rate of incorporation of tracer [13C]valine into albumin increased by 73% to 0.433 +/- 0.129%/h (P < 0.05); the apparent protein synthetic rate calculated from the incorporation of leucine applied during the flood was 0.402 +/- 0.057 (P < 0.001). These results raise further doubts about the validity of the flooding dose method for the measurement of rates of human protein synthesis.

A novel and convenient method of delayed primary skin closure for grossly contaminated abdominal wounds.

We describe a new method of delayed primary closure for grossly contaminated abdominal surgical wounds, combining the reduced vulnerability to infection associated with delayed skin closure and the excellent cosmesis of subcuticular suture. The surgical technique is outlined and the results in nine patients with gross intra-abdominal sepsis reported.

Flooding with L-[1-13C]leucine stimulates human muscle protein incorporation of continuously infused L-[1-13C]valine.

To investigate why flooding methods give higher rates than constant-infusion methods for muscle protein synthesis, we studied seven healthy postabsorptive male volunteers (20-42 yr; 67-74 kg) during a 7.5-h primed constant infusion of L-[1-13C]valine (99 atoms %, 1.5 mg/kg prime, 1.5 mg.kg-1.h-1); at 6.5 h they were given a flood of L-[1-13C]leucine (20 atoms %, 0.05 g/kg). Musculus tibialis anterior biopsies were taken at 0.5, 6, and 7.5 h, and blood was sampled as appropriate. The enrichment of valine and leucine in muscle protein (isotope ratio mass spectrometry of protein amino acid-derived 13CO2) was compared with the average enrichment of various amino acid pools (gas chromatography-mass spectrometry). During infusion of [13C] valine the rate of muscle protein synthesis measured using alpha-ketoisovalerate (alpha-KIV) as precursor surrogate was 0.043 +/- 0.002%/h (SE). After flooding with leucine, the incorporation rate of [13C]valine increased by 70% (P less than 0.05), i.e., apparent muscle protein synthetic rate (based on alpha-[13C]KIV) increased to 0.065 +/- 0.009%/h (P less than 0.05); the rate calculated from the [13C]leucine flood was 0.060 +/- 0.005%/h (P less than 0.01). The synthetic rates calculated using the constant-infusion method were higher after flooding, irrespective of the precursor chosen, raising serious concern about the validity of the flooding-dose method.

Perineural tumour spread: an unusual cause of carpal tunnel syndrome.

We describe the development of the carpal tunnel syndrome in a 58-year-old man, from perineural spread of a previously-excised cutaneous malignancy.