Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1-BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.

Mucosal Adenoviral-vectored Vaccine Boosting Durably Prevents XBB.1.16 Infection in Nonhuman Primates.

Waning immunity and continued virus evolution have limited the durability of protection from symptomatic infection mediated by intramuscularly (IM)-delivered mRNA vaccines against COVID-19 although protection from severe disease remains high. Mucosal vaccination has been proposed as a strategy to increase protection at the site of SARS-CoV-2 infection by enhancing airway immunity, potentially reducing rates of infection and transmission. Here, we compared protection against XBB.1.16 virus challenge 5 months following IM or mucosal boosting in non-human primates (NHP) that had previously received a two-dose mRNA-1273 primary vaccine regimen. The mucosal boost was composed of a bivalent chimpanzee adenoviral-vectored vaccine encoding for both SARS-CoV-2 WA1 and BA.5 spike proteins (ChAd-SARS-CoV-2-S) and delivered either by an intranasal mist or an inhaled aerosol. An additional group of animals was boosted by the IM route with bivalent WA1/BA.5 spike-matched mRNA (mRNA-1273.222) as a benchmark control. NHP were challenged in the upper and lower airways 18 weeks after boosting with XBB.1.16, a heterologous Omicron lineage strain. Cohorts boosted with ChAd-SARS-CoV-2-S by an aerosolized or intranasal route had low to undetectable virus replication as assessed by levels of subgenomic SARS-CoV-2 RNA in the lungs and nose, respectively. In contrast, animals that received the mRNA-1273.222 boost by the IM route showed minimal protection against virus replication in the upper airway but substantial reduction of virus RNA levels in the lower airway. Immune analysis showed that the mucosal vaccines elicited more durable antibody and T cell responses than the IM vaccine. Protection elicited by the aerosolized vaccine was associated with mucosal IgG and IgA responses, whereas protection elicited by intranasal delivery was mediated primarily by mucosal IgA. Thus, durable immunity and effective protection against a highly transmissible heterologous variant in both the upper and lower airways can be achieved by mucosal delivery of a virus-vectored vaccine. Our study provides a template for the development of mucosal vaccines that limit infection and transmission against respiratory pathogens.

The ambiguous ripening nature of the fig (Ficus carica L.) fruit: a gene-expression study of potential ripening regulators and ethylene-related genes.

The traditional definition of climacteric and non-climacteric fruits has been put into question. A significant example of this paradox is the climacteric fig fruit. Surprisingly, ripening-related ethylene production increases following pre- or postharvest 1-methylcyclopropene (1-MCP) application in an unexpected auto-inhibitory manner. In this study, ethylene production and the expression of potential ripening-regulator, ethylene-synthesis, and signal-transduction genes are characterized in figs ripening on the tree and following preharvest 1-MCP application. Fig ripening-related gene expression was similar to that in tomato and apple during ripening on the tree, but only in the fig inflorescence-drupelet section. Because the pattern in the receptacle is different for most of the genes, the fig drupelets developed inside the syconium are proposed to function as parthenocarpic true fruit, regulating ripening processes for the whole accessory fruit. Transcription of a potential ripening regulator, FcMADS8, increased during ripening on the tree and was inhibited following 1-MCP treatment. Expression patterns of the ethylene-synthesis genes FcACS2, FcACS4, and FcACO3 could be related to the auto-inhibition reaction of ethylene production in 1-MCP-treated fruit. Along with FcMADS8 suppression, gene expression analysis revealed upregulation of FcEBF1, and downregulation of FcEIL3 and several FcERFs by 1-MCP treatment. This corresponded with the high storability of the treated fruit. One FcERF was overexpressed in the 1-MCP-treated fruit, and did not share the increasing pattern of most FcERFs in the tree-ripened fig. This demonstrates the potential of this downstream ethylene-signal-transduction component as an ethylene-synthesis regulator, responsible for the non-climacteric auto-inhibition of ethylene production in fig.

Factors associated with empyema in children with community acquired pneumonia.

AIM: Empyema is a potential complication of community acquired pneumonia but factors predicting this complication are lacking. METHODS: A retrospective study of all previously healthy pediatric patients admitted between January 2007 and July 2009 with CAP. Patients with non-lobar pneumonia, RSV bronchiolitis, underlying chronic disease, or hospital-acquired pneumonia were excluded. Preadmission, clinical characteristics on admission, and outcome were compared between patients with and without empyema. Management strategies in patients with empyema were also compared. RESULTS: Overall 356 patients were included. Median age was 3.8 ± 3.54 years and 60.7% were males. A total of 43 patients (12%) were diagnosed with empyema. The development of empyema was independently associated, on multivariate analysis, with older age, female gender and antibiotic therapy prior to admission, and with dyspnea, thrombocytopenia and involvement of more than one lobe on chest radiograph on admission. Patients who developed empyema had a longer and more complicated course. Hypoxemia on admission was significantly less frequent in patients with empyema who were treated with antibiotic therapy alone, compared to those treated with chest tube or video-assisted thoracoscopic surgery. CONCLUSION: Early identification of dyspnea and thrombocytopenia in patients with community acquired pneumonia could alert physicians on the potential development of empyema. Antibiotic therapy alone may be sufficient in patients with empyema who are mildly hypoxemic on admission.

Reevaluation of presentation and course of idiopathic intracranial hypertension--a large cohort comprehensive study.

OBJECTIVES: We analyzed the clinical and ophthalmological findings in a large group of patients with idiopathic intracranial hypertension (IIH) trying to find factors that might influence the course of the disease. MATERIALS AND METHODS: Medical records of patients with IIH were retrospectively reviewed. The patients included were women after menarche and men older than 18 years of age who were followed up for at least 1 year. RESULTS: Eighty-two patients (89% women) with a mean age of 30.2 ± 12.0 years were included. The prevailing complaint was headache and transient visual obscurations followed by tinnitus and double vision. Eighty-two percent of patients were overweight at the time of diagnosis. Overweight patients had higher opening cerebrospinal fluid (CSF) pressure than patients with normal weight did. The grade of papilledema correlated with the CSF opening pressure. Inverse correlation was found between the depression of the visual field sensitivity and the grade of papilledema. The mean follow-up time was 61.3 ± 62.3 months. Eighty-four percent of the patients have improved while in 22% CSF diversion procedures or optic nerve decompression was required. The mean body mass index (BMI) at the end of follow-up decreased significantly. Sixty-seven percent of the patients suffered a recurrence of IIH. The number of recurrences inversely correlated with weight loss. Visual field defects on presentation were encountered more frequently in patients with recurrence. Women with recurrence had a history of more pregnancies. CONCLUSIONS: Our results confirm the strong association between overweight and IIH. The recurrence rate seemed to be influenced by the obstetrical history and the severity of visual field defects at presentation. In contrast to some previous studies, we have found an interrelation between the CSF opening pressure, grade of papilledema and depression of the visual field sensitivity.

A comparative study of the postoperative allogeneic blood-sparing effects of tranexamic acid and of desmopressin after total knee replacement.

BACKGROUND: Tissue hypoxia and reperfusion induce abnormal hemostatic function. Therefore, bleeding after total knee replacement (TKR) may be a result of a tourniquet-induced imbalance of the procoagulant and fibrinolytic systems. Because laboratory confirmation of tourniquet-induced abnormal hemostasis is difficult to obtain, indirect evidence must be sought. STUDY DESIGN AND METHODS: A prospective, single-blind study of 40 patients undergoing TKR was performed. In the tranexamic acid (TA) group, in the 30 minutes before the limb tourniquet was deflated, an IV bolus dose of TA (15 mg/kg) was administered. Thereafter, a constant IV infusion of 10 mg per kg per hour was administered until 12 hours after tourniquet deflation. In the desmopressin group, desmopressin (0.3 mg/kg) and saline were administered by a similar protocol. No blood was administered intraoperatively. A postoperative Hct <27 percent constituted the postoperative transfusion trigger. Patients were examined daily for signs of lower-limb deep vein thrombosis, and they underwent lower-limb Doppler ultrasound on postoperative Day 5. Three months after surgery, the incidence of delayed thromboembolic events was assessed. RESULTS: During the first 12 postoperative hours, blood accumulation in the surgical drain was significantly (p<0.05) lower in the TA group (162 mL +/- 129) than in the desmopressin group (342 mL +/- 169). From the sixth postoperative hour until 3 days postoperatively, Hct levels were significantly lower in the desmopressin group than in the TA group. Significantly more allogeneic blood was transfused in the desmopressin group (11 patients received 16 units) than in the TA group (3 patients each received 1 unit) (p<0.02). There were no clinical signs of deep vein thrombosis or abnormal Doppler ultrasound studies. Three months postoperatively, there were no thromboembolic events among the 37 patients interviewed. CONCLUSION: TA induces better blood sparing than desmopressin. Therefore, a tourniquet-induced increase in fibrinolysis is the likely cause of delayed bleeding after TKR surgery. However, before routine administration, the effect of TA on the incidence of thromboembolic events requires further investigation.

The analgesic efficacy of patient-controlled bupivacaine wound instillation after total abdominal hysterectomy with bilateral salpingo-oophorectomy.

UNLABELLED: To assess the effect of local anesthetic wound instillation on visceral and somatic pain, we studied 36 patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy. A standard general anesthetic was administered. On completion of the operation, a multiorifice 20-gauge epidural catheter was placed above the superficial abdominal fascia such that the tip was at the midpoint of the surgical wound. After surgery, either bupivacaine 0.25% (Bupivacaine group) or sterile water (Control group) was administered via a patient-controlled analgesia device programmed to deliver 9.0 mL with a 60-min lockout interval. During the first 6 h after surgery, rescue IV morphine (2 mg) was administered every 10 min until a visual analog scale score of <30 mm was achieved. Thereafter, on patient request, rescue meperidine 1 mg/kg IM was administered. When compared with the Control group, significantly (P < 0.001) less rescue analgesia was administered to patients in the Bupivacaine group. Rescue morphine administered during the first 6 h after surgery was 6 +/- 4 mg versus 12 +/- 6 mg (P < 0.001) for the Bupivacaine and Control groups, respectively. Rescue meperidine administered was 29 +/- 37 mg versus 95 +/- 36 mg (P < 0.001) for the Bupivacaine and Control groups, respectively. Nausea and antiemetic drug administration was significantly (P = 0.003) less in the Bupivacaine group. Pain scores were similar between the groups. Patient satisfaction was significantly (P = 0.04) more in the Bupivacaine group. We conclude that bupivacaine wound instillation decreases opioid requirements and nausea in the first 24 h after total abdominal hysterectomy with bilateral salpingo-oophorectomy. IMPLICATIONS: Bupivacaine instillation via an electronic patient-controlled analgesia device provides effective analgesia after total abdominal hysterectomy with bilateral salpingo-oophorectomy.

Bupivacaine wound instillation via an electronic patient-controlled analgesia device and a double-catheter system does not decrease postoperative pain or opioid requirements after major abdominal surgery.

UNLABELLED: To assess the analgesic efficacy of patient-controlled bupivacaine wound instillation, 50 patients undergoing major intraabdominal surgery were enrolled into this prospective, placebo-controlled, double-blinded study. In all cases, a standard general anesthetic was administered. On completion of surgery, two multihole 20-gauge epidural catheters were tunneled through the proximal and distal apices of the surgical wound and placed above the fascia such that the tips were at the margin of the first and second thirds of the surgical wound, respectively. Postoperatively, a patient-controlled analgesia (PCA) device was connected to the instillation system. Either bupivacaine 0.25% (Bupivacaine Group) or an equal volume of sterile water (Control Group) was administered. The PCA device was programmed to deliver 9.0 mL with a 60-min lockout interval and no basal infusion. During the first six postoperative hours, a coinvestigator administered "rescue" morphine (2 mg IV). Thereafter, meperidine 1 mg/kg IM was administered on patient request for additional analgesia. Instillation attempts and actual number of injections were similar between the groups. The mean number of pump infusions and the mean "rescue" opioid requirements during the 24-h study period were similar between the groups. The total "rescue" morphine administered during the first six postoperative hours was 16 +/- 17 mg vs 18 +/- 14 mg for the Bupivacaine and Control Groups, respectively. The total meperidine administered during this period was 1.6 +/- 1.4 mg/kg and 2 +/- 1.2 mg/kg for the Bupivacaine and Control Groups, respectively. Preoperatively, hourly for the first six postoperative hours, and on removal of the instillation catheter, patient-generated visual analog scales for pain were similar at rest, on coughing, and after leg raise. In conclusion, bupivacaine wound instillation via an electronic PCA device and a double-catheter system does not decrease postoperative opioid requirements after surgery performed through a midline incision. IMPLICATIONS: After major abdominal surgery performed through a 20-cm incision, repeated 0.25% bupivacaine wound instillation via an electronic patient-controlled analgesia device and a double-catheter system does not decrease postoperative pain or opioid requirements.

The analgesic efficacy of patient-controlled ropivacaine instillation after Cesarean delivery.

To assess the efficacy and safety of wound instillation of ropivacaine, when administered via a patient-controlled elastometric pump, 50 term parturients undergoing cesarean delivery were enrolled into this prospective, placebo-controlled, double-blinded study. In all cases, a standard spinal anesthetic was administered. After the surgery, a multihole 20-gauge epidural catheter (B. Braun, Melsungen, Germany) was placed above the fascia such that the tip was sited at the point that demarcated 50% of the length of the surgical wound. Thereafter, the catheter was connected to the elastometric pump. According to a computer-generated randomization schedule, the pump was filled with either ropivacaine 0.2% (Ropivacaine Group) or an equal volume of sterile water (Control Group). Postoperatively, patient-controlled analgesia was administered via the elastometric pump. During the first 6 postoperative hours, a coinvestigator administered "rescue" morphine (2 mg, IV). Thereafter, "rescue" dipyrone (1 g) was administered on patient request. In a subset of 10 patients, blood ropivacaine levels were assessed. Compared with the Control Group, significantly fewer patients in the Ropivacaine Group received "rescue" morphine (92% vs. 48%, respectively) (P<0.01). The total "rescue" morphine administered during the first 6 postoperative hours was 2+/-3 mg vs. 10+/-5 mg (P<0.01) for the Ropivacaine and Control Groups, respectively. Patient-generated resting pain scores were similar between the groups. However, pain scores generated after coughing and leg raise were significantly (P<0.04) less in the Ropivacaine Group. More patients in the Ropivacaine Group than in the Control Group described their analgesia as good or excellent. In the subset of patients (n = 10) studied, unbound ropivacaine blood levels were below the toxic threshold (600 ng/mL). However, blood ropivacaine accumulation was noted. All patients stated that the elastometric pump was easy to use. Ropivacaine wound instillation via an elastometric pump is a simple technique that provides safe and effective analgesia after cesarean delivery.

Video-assisted transthoracic sympathectomy in the treatment of primary hyperhidrosis: friend or foe?

The authors hypothesize that palmar hyperhidrosis is a systemic manifestation of abnormal sudomotor function; consequently, thoracoscopic sympathectomy to alleviate symptoms in the hands may result in heat dissipation because sweating is transferred to other sites. To investigate this phenomenon and to determine whether it adversely affects patient satisfaction, a standard questionnaire was administered to 626 patients who underwent sympathectomy at a university-associated public hospital between 1991 and 1998; only patients treated at least 6 months before questionnaire distribution were included in the study. Replies were received from 336 (53.7%) individuals. The surveyed patients underwent bilateral T2, T3 (palmar sweating), or T3, T4 (axillary sweating) sympathectomy by a standard video-assisted transthoracic technique. Main outcome measures included the incidence of dry hands, compensatory sweating, chest pain, upper-limb muscle weakness, shortness of breath, and gustatory phenomena; in addition, patient perception of the success of the surgical procedure was assessed. After sympathectomy, 97.3% (P < 0.0001) and 29.2% (P < 0.001) of patients reported significant improvement in palmar hyperhidrosis and axillary sweating, respectively. Postsurgery, severe compensatory sweating was experienced in 90% of patients (P < 0.0001). The sites of compensatory sweating were the back (75%), abdomen (51%), feet (23%), groin and thigh (13%), chest (13%), and axillae (8%). Transient whole-body sweating for no apparent reason was experienced in 30% of patients. Thirty-seven patients (11%) regretted having undergone the surgical procedure. In contrast, 25% and 64% of patients were either satisfied or very satisfied with the outcome of the procedure. From the survey results, the authors conclude that palmar hyperhidrosis is a systemic manifestation of abnormal sudomotor function and that thoracic sympathectomy may alleviate symptoms in a large proportion of patients. However, for some individuals, compensatory sweating may prove to be an equally troublesome handicap. Because the occurrence of severe compensatory sweating is unpredictable, a reversible sympathectomy may be desirable.

Continuous intravenous diclofenac does not induce opioid-sparing or improve analgesia in geriatric patients undergoing major orthopedic surgery.

STUDY OBJECTIVE: To assess the analgesic efficacy and perioperative opioid-sparing effects of adjuvant intravenous (IV) diclofenac. DESIGN: Prospective, controlled, double-blind study. SETTING: Large referral hospital. PATIENTS: 40 ASA physical status I, II, and III geriatric patients (>65 years) undergoing open reduction and internal fixation of subcapital fracture of the femur. INTERVENTIONS: A standardized general anesthetic was administered. On induction of anesthesia, patients in the diclofenac group received an IV bolus of diclofenac (0.7 mg/kg) followed by a constant infusion (0.15 mg/kg/hr) until the end of surgery. In the saline group, an equal volume of saline was administered. "Rescue" fentanyl was administered in response to an increase in mean arterial pressure or heart rate (exceeding 20% of the patient's preinduction "baseline" values) that did not respond to a 30% increase in the inspired isoflurane concentration. Postoperative pain was assessed using a four-point patient-generated pain score (1 = none, 2 = mild, 3 = moderate, 4 = severe) as well as number of attempts and actual morphine delivered via a patient-controlled analgesia (PCA) device. MEASUREMENTS AND MAIN RESULTS: The two treatment groups were demographically comparable. The perioperative hemodynamic variables, as well as the induction and "rescue" fentanyl dosages, were unaffected by the treatment modality. Pain scores, PCA attempts, and actual morphine delivered were statistically similar between the two groups. CONCLUSIONS: Adjuvant IV diclofenac does not improve intraoperative stability or decrease postoperative opioid requirements in geriatric patients undergoing internal fixation of subcapital fracture of the femur.

A comparative study of the postoperative allogeneic blood-sparing effect of tranexamic acid versus acute normovolemic hemodilution after total knee replacement.

UNLABELLED: Both acute normovolemic hemodilution (NVHD) and tranexamic acid (TA) are potentially useful allogeneic blood conservation strategies after total knee replacement. However, the relative efficacy of these blood-sparing techniques is unknown. Therefore, to compare the postoperative allogeneic blood sparing of NVHD and TA after total knee replacement, we investigated 40 patients in a prospective, single-blinded study protocol. In Group TA, 30 min before deflating the limb tourniquet, an IV infusion of TA, 15 mg/kg, was administered over a 30-min period. Thereafter, a constant IV infusion of 10 mg x kg(-1) x hr(-1) was administered until 12 h after deflation of the limb tourniquet. Before induction of anesthesia, NVHD patients were bled to a target hematocrit of approximately 28%. Intravascular blood volume was maintained with lactated Ringer's solution. All autologous blood was transfused at the end of the surgery. Postoperatively, hematocrit was measured daily. In all cases, a hematocrit <27% was the postoperative transfusion trigger. Before discharge, deep vein thrombosis was excluded by Echo Doppler. Three months after surgery, the incidence of delayed thromboembolic events was assessed. The two groups were demographically comparable. In Group NVHD, 843 mL+/-289 of autologous blood was removed. Despite autologous blood transfusion, during the early postoperative period and until the third postoperative day, the NVHD group had significantly (P < 0.01) lower mean hematocrits when compared with the TA group. Thereafter, because of a significantly (P < 0.0008) greater allogeneic blood requirement in the NVHD group, no statistically significant difference in mean hematocrit recordings was noted among the groups. Blood accumulation in the surgical drain 12 h postoperatively, was significantly (P < 0.0008) higher in the NVHD group (259 mL+/-156) when compared with the TA group (110 mL+/-62). Significantly (P < 0.0008) more allogeneic blood was transfused in the NVHD group (19 U/13 patients) when compared with the TA group (2 U/2 patients). No abnormal Echo Doppler studies were reported. During the 3-mo follow-up period, a deep vein thrombosis and pulmonary embolus were documented in one patient in the NVHD group. We conclude that perioperative hemodynamic stability and allogeneic blood sparing is superior after tranexamic acid administration when compared with normovolemic hemodilution. IMPLICATIONS: For total knee replacement, when compared with normovolemic hemodilution, tranexamic acid administration is associated with superior perioperative hemodynamic stability and allogeneic blood sparing.

The effect of midazolam premedication on mental and psychomotor recovery in geriatric patients undergoing brief surgical procedures.

UNLABELLED: To assess the effect of IV midazolam premedication on recovery of cognitive function, 90 geriatric patients (aged 65-81 yr) undergoing brief transurethral procedures were enrolled into this prospective, placebo-controlled, double-blinded study. In all cases, a standard general anesthetic was administered. Thirty minutes before operating room transfer, patients in Group 0.5 mg, Group 2 mg, and Group S received 0.5 mg of midazolam, 2 mg of midazolam, or an equal volume of saline, respectively. Before study-drug administration (baseline), at 15 min thereafter, as well as on arrival in the postanesthesia care unit (PACU), and at 60 min and 120 min, postoperatively, we administered a digit-symbol substitution test, a mini-mental test, a shape-sorter test, and a patient-generated 100-mm visual analog score (0 = minimal and 100 = maximal) for anxiety, sleepiness, and coordination. A 4-point scale was used to assess the degree of patient sedation at 7, 15, and 30 min after study-drug administration. Using a modified Aldrete scoring system, PACU discharge was determined by the PACU staff. Patient anxiety, sleepiness, and coordination scores at baseline and at 15 min after study-drug administration were similar. When compared with saline, midazolam was associated with a significantly (P < 0.05) higher incidence of "deep" sedation. In Group 2 mg, the incidence of a low preoperative Spo2 (<94%) was significantly (P < 0.05) higher when compared with Group S. Emergence, extubation, and orientation times, as well as time to follow commands were unaffected by midazolam premedication. Postoperatively, the digit-symbol substitution test, mini-mental test, and shape-sorter test were similar among the groups. However, time to PACU discharge was significantly (P = 0.03) longer in the two midazolam treatment groups (41 +/-25 min, 60 +/- 32 min, 53 +/- 39 min for Groups S, 0.5 mg, and 2 mg, respectively). Finally, patient satisfaction was unaffected by the randomization schedule. IMPLICATIONS: IV premedicant midazolam 0.5 mg or 2 mg does not adversely affect mental and psychomotor recovery in geriatric patients undergoing brief surgical procedures. However, midazolam administration significantly prolonged postanesthesia care unit discharge time. Finally, during the preoperative period, midazolam increases the incidence of a Spo2 <94% in a dose-dependent manner.

Effect of spinal versus general anesthesia on bladder compliance and intraabdominal pressure during transurethral procedures.

STUDY OBJECTIVE: To evaluate the influence of spinal versus general anesthesia on bladder compliance and intraabdominal pressure in elderly males undergoing elective transurethral resection of the prostate. DESIGN: Prospective, randomized, open-label study. SETTING: Teaching hospital. PATIENTS: 21 ASA physical status I, II, and III patients at least 18 years of age, undergoing transurethral surgery. INTERVENTIONS: According to a computer-generated randomization schedule, patients were allocated to one of two groups. In Group Spinal (S), 10 mg of hyperbaric tetracaine was administered intrathecally. In Group General Anesthesia (GA), patients received, fentanyl intravenous (i.v. 1 to 2 micrograms/kg and propofol i.v. 1.0 to 2.0 mg/kg for induction of anesthesia. Thereafter, a laryngeal mask airway was inserted and, with spontaneous ventilation, anesthesia was maintained by administering isoflurane (end-tidal 0.7% to 1.2%) and 70% nitrous oxide (N2O) in oxygen. Intraabdominal pressure and bladder compliance were recorded prior to the induction of anesthesia and immediately before the onset of the surgical procedure. MEASUREMENTS AND MAIN RESULTS: The two groups were demographically comparable. In Group S, mean bladder compliance was significantly (p = 0.003) higher and mean intraabdominal pressure significantly lower (p = 0.007) when compared to baseline preanesthetic values. In Group GA, mean intraabdominal pressure significantly (p = 0.006) decreased when compared to baseline preanesthetic recordings. Following the induction of general anesthesia, a small change in bladder compliance was noted. However, statistical significance was not reached. Data were analyzed and compared using Student's t-test (p < 0.05 was considered statistically significant). CONCLUSION: Both spinal and general anesthesia induced a significant decrease in intraabdominal pressure. While both techniques were associated with an increase in bladder compliance, statistical significance was demonstrated only in the spinal anesthesia treatment group.

The effect of repeated epidural sympathetic nerve block on "failed back surgery syndrome" associated chronic low back pain.

STUDY OBJECTIVE: To assess the therapeutic benefits of repeated epidural local anesthetic administration on pain perception and straight leg raise (SLR) in patients suffering from chronic low back pain. DESIGN: Prospective, randomized, controlled, single-blind study protocol. PATIENTS: 50 ASA physical status I, II, and III patients at least 18 years of age, who had previously undergone spine surgery. INTERVENTIONS: All participants were admitted to hospital for the 5-day duration of the study. Following epidural catheterization, fluoroscopy was performed to verify correct placement of the epidural catheter. On the first study day, all patients received depomedrol 80 mg, in 10-ml 1% lidocaine, epidurally. Thereafter, patients were randomized into two equal groups. In Group Bupivacaine (B) 10-ml 0.125% bupivacaine was administered. In Group Saline (S), an equal volume of saline was administered. Epidural injections were performed twice daily (09H00 and 14H00) for 4 days. Sympathetic blockade was confirmed by the presence of peripheral vasodilatation. Sensory blockade was assessed using loss of pin prick and temperature sensation. SLR as well as patient-generated 100-mm visual analog score (VAS) for pain were performed prior to each injection, at 15 minutes after injection, and hourly for 2 hours thereafter. Similar parameters were measured 1 week, 1 month, and 3 months after discharge. MEASUREMENTS AND MAIN RESULTS: 46 patients completed the study. VAS for pain was marginally lower in Group B. However, statistical significance was not demonstrated. During the hospitalization period, the SLR in both study groups significantly (0.008) improved with time. However, no difference between the groups was demonstrated. In both groups, 1 week, 1 month, and 3 months after discharge, the SLR was comparable to prestudy recordings. In Group B, at 1 week, 1 month, and 3 months after discharge, patient-generated VAS for pain were significantly (p = 0.002) higher when compared to pain scores at the time of patient discharge.

Epidural steroids for treating "failed back surgery syndrome": is fluoroscopy really necessary?

UNLABELLED: Epidural steroids are commonly administered in the treatment of "failed back surgery syndrome." Because patient response is dependent on accurate steroid placement, fluoroscopic guidance has been advocated. However, because of ever-increasing medical expenditures, the cost-benefit of routine fluoroscopy should be critically evaluated. Therefore, 50 patients were enrolled into this institutional review board-approved, prospective, controlled, single-blinded study. At a predetermined intervertebral level, the epidural space was identified using an air loss of resistance technique. Thereafter, an epidural catheter was inserted 2 cm through the epidural needle. To determine the accuracy of the clinical placement, contrast medium was administered through the epidural catheter; antero-posterior and lateral lumbar spine radiographs were then obtained. The number of attempts required to successfully locate the epidural space, the reliability of the air loss of resistance technique in indicating successful epidural penetration in failed back surgery syndrome, the ability of the clinician to accurately predict the intervertebral space at which the epidural injection was performed, and the spread of contrast medium within the epidural space were recorded. A total of 48 epidurograms were performed. The number of attempts to successfully enter the epidural space was 2 +/- 1. In 44 cases, the radiological studies confirmed the clinical impression that the epidural space had been successfully identified. In three patients, the epidural catheter was in the paravertebral tissue. One myelogram was recorded. In 25 patients, the epidural catheter did not pass through the predetermined intervertebral space. In 35 cases, the contrast medium did not reach the level of pathology. IMPLICATIONS: The clinical sign of loss of resistance is a reliable indicator of epidural space penetration in most cases of "failed back surgery syndrome." However, surface anatomy is unreliable and may result in inaccurate steroid placement. Finally, despite accurate placement, the depot-steroid solution will spread to reach the level of pathology in only 26% of cases.

Diclofenac does not decrease renal blood flow or glomerular filtration in elderly patients undergoing orthopedic surgery.

UNLABELLED: Nonsteroidal antiinflammatory drugs (NSAIDs) have become increasingly popular in the treatment of perioperative pain. Due to concerns that cyclooxygenase inhibition may adversely affect renal function, these drugs are often not used in geriatric surgical patients. However, the perioperative effect of NSAIDs on renal blood flow (RBF) and glomerular filtration rate (GFR) has not been assessed. Therefore, using a prospective, controlled, double-blinded study design, we evaluated the effect of diclofenac on RBF and GFR in 20 patients (>65 yr) undergoing open reduction and internal fixation of the femur. All patients were normovolemic before the study. A standardized general anesthetic was administered. On induction of anesthesia, patients in the diclofenac group received an IV bolus of diclofenac (0.7 mg/kg) followed by a constant infusion (0.15 mg x kg(-1) x h(-1)) until the end of surgery. In the saline group, an equal volume of saline was administered. During four time periods (equilibration, anesthesia, surgical, recovery), GFR and effective renal plasma flow (ERPF) were measured by inulin and paraaminohippurate clearance, respectively. After the induction of anesthesia and throughout the surgical period, ERPF and GFR were significantly decreased compared with preoperative baseline values. However, no difference was demonstrated between the groups. These results suggest that, in geriatric surgical patients, the adjuvant administration of NSAIDs does not adversely affect renal function. IMPLICATIONS: As determined by inulin and paraaminohippurate clearance, the intraoperative administration of diclofenac does not decrease glomerular filtration rate or effective renal plasma flow in normovolemic geriatric patients. Therefore, diclofenac may be administered during the perioperative period.

Influence of thiopental and propofol on postoperative cognitive recovery in the elderly patient undergoing general anesthesia.

STUDY OBJECTIVE: To assess mental and psychomotor recovery following induction of anesthesia with thiopental or propofol in elderly patients undergoing general anesthesia. DESIGN: Randomized, prospective, double-blind study. SETTING: Large referral hospital. PATIENTS: 40 elderly patients ASA physical status I-III (> 65 years) undergoing abdominopelvic surgery with an estimated surgical time of at least 90 minutes. INTERVENTIONS: All patients received combined epidural-general anesthesia. After establishing a T6 sensory blockade, patients were randomized to receive either thiopental or propofol for induction of general anesthesia. The induction drug was slowly titrated until loss of eyelash reflex was noted. Thereafter, all patients received desflurane (2% to 3% end-tidal) and 70% nitrous oxide (N2O) in oxygen for maintenance of general anesthesia. To facilitate tracheal intubation, intravenous alfentanil 10 micrograms/kg and atracurium 0.4 mg/kg were administered. Perioperative analgesia was maintained with epidural bupivacaine. MEASUREMENTS AND MAIN RESULTS: A digit substitution test (DSST) and shape-sorter test, as well as patient-generated 100-mm visual analog score (VAS; 0 = minimal and 100 = maximal) for anxiety, sleepiness, and coordination, were performed during the preanesthetic interview, on postanesthesia care unit admission, and at 15, 45, 90, and 120 minutes thereafter. To induce loss of consciousness, either thiopental 2.5 +/- 1.0 mg/kg or propofol 1.6 +/- 0.6 mg/kg was administered. The mean anesthetic time was 109 +/- 30 minutes and 114 +/- 38 minutes for the thiopental and propofol groups, respectively. Emergence, extubation, and orientation times, as well as time to follow commands, were unaffected by patient randomization. Similarly, the DSST and shape-sorter tests, in addition to the patient-generated VAS for pain, anxiety, and coordination, were similar among groups. However, irrespective of treatment modality, return to baseline digit substitution and shape-sorter scores were significantly delayed (p < 0.01). CONCLUSION: When compared to thiopental, propofol does not facilitate improved cognitive recovery in geriatric patients undergoing prolonged surgery.

The induction, maintenance, and recovery characteristics of spinal versus general anesthesia in elderly patients.

STUDY OBJECTIVE: To compare the induction and recovery profiles of three combinations of general anesthesia when used as an alternative to spinal anesthesia for elderly patients. DESIGN: Randomized, prospective, open-label study. SETTING: Large referral hospital. PATIENTS: 100 [ASA physical status I, II, and III] patients over 60 years of age undergoing brief transurethral surgery. INTERVENTIONS: In Groups Propofol-Propofol (P-P), Propofol-Isoflurane (P-I), and Propofol-Desflurane (P-D), anesthesia was induced with fentanyl (1 to 2 micrograms/kg i.v.) and propofol (1.0 to 2.0 mg/kg i.v.) and maintained with 70% nitrous oxide in oxygen and either a propofol infusion (75 to 150 micrograms/kg/min) or isoflurane (end-tidal 0.7% to 1.2%) or desflurane (end-tidal 1% to 4%), respectively. After induction, a laryngeal mask airway was placed and spontaneous ventilation was maintained. In Group Spinal (S), 1.5 ml 4% lidocaine (60 mg), in an equal volume of 10% dextrose, was administered intrathecally. MEASUREMENTS AND MAIN RESULTS: Induction and recovery characteristics were compared. Induction with propofol was technically easier and significantly (medp < 0.0001) faster (4.6 +/- 1.7 min, 4.7 +/- 2.2 min, and 3.8 +/- 1.4 min for Groups P-P, P-I, and P-D, respectively) than induction of spinal anesthesia (9.3 +/- 3.4 min). During the induction period, mean arterial blood pressure and heart rate were significantly higher in Group S. Emergence, extubation, and orientation times were similar among the general anesthesia treatment groups. In Group S, patient-generated pain scores were lower (p < 0.05) and recovery room admission longer (p < 0.001). Time to return to baseline digit symbol substitution test (DSST) scores was marginally improved in Groups P-P and P-D when compared to Group P-I. Postoperative nausea, sleepiness, anxiety, and coordination were unaffected by the treatment modality. CONCLUSION: General anesthesia with propofol and desflurane facilitates shorter induction and recovery times without adversely affecting patient comfort. Therefore, this technique may be preferable to spinal anesthesia for elderly patients undergoing short transurethral surgical procedures.