Persistent Oliguria Research Articles

Safety and efficacy of continuous renal replacement therapy for children less than 10 kg using standard adult machines

Continuous Renal Replacement Therapy (CRRT) machines are used off-label in patients less than 20 kg. Infant and neonates-dedicated CRRT machines are making their way into current practice, but these machines are available only in select centres. This study assesses the safety and efficacy of CRRT using adult CRRT machines in children ≤ 10 kg and to determines the factors affecting the circuit life in these children. Design: Retrospective cohort study of children ≤ 10 kg who received CRRT (January 2010-January 2018) at a PICU in a tertiary care centre in London, UK. Primary diagnosis, markers for illness severity, CRRT characteristics, length of PICU admission and survival to PICU discharge were collected. Descriptive analysis compared survivors and non-survivors. A subgroup analysis compared children ≤ 5 kg to children 5–10 kg. Fifty-one patients ≤ 10 kg received 10,328 h of CRRT, with median weight of 5 kg. 52.94% survived to hospital discharge. Median circuit life was 44 h (IQR 24–68). Bleeding episodes occurred with 6.7% of sessions and hypotension for 11.9%. Analysis of efficacy showed a reduction in fluid overload at 48 h (P = 0.0002) and serum creatinine at 24 and 48 h (P = 0.001). Blood priming was deemed to be safe as serum potassium decreased at 4 h (P = 0.005); there was no significant change in serum calcium. Survivors had a lower PIM2 score at PICU admission (P < 0.001) and had longer PICU length of stay (P < 0.001). Conclusion: Pending neonatal and infant dedicated CRRT machines, CRRT can be safely and effectively applied to children weighing ≤ 10 kg using adult-sized CRRT machines.What is Known:• Continuous Renal Replacement Therapy can be used for a variety of renal and non-renal indications to improve outcomes for children in the paediatric intensive care unit. These include, persistent oliguria, fluid overload, hyperkalaemia, metabolic acidosis, hyperlactatemia, hyperammonaemia, and hepatic encephalopathy.• Young children ≤ 10 kg are most often treated using standard adult machines, off-label. This potentially places them at risk of side effects due to high extracorporeal circuit volumes, relatively higher blood flows, and difficulty in achieving vascular access.What is New:• This study found that standard adult machines were effective in reducing fluid overload and creatinine in children ≤ 10 kg. This study also assessed safety of blood priming in this group and found no evidence of an acute fall in haemoglobin or calcium, and a fall in serum potassium by a median of 0.3 mmol/L. The frequency of bleeding episodes was 6.7%, and hypotension requiring vasopressors or fluid resuscitation occurred with 11.9% of treatment sessions.• These findings suggest that adult CRRT machines are sufficiently safe and efficacious for routine use in PICU for children ≤ 10 kg and suggest that further research is undertaken, regarding the routine rollout of dedicated machines.

Efficacy of gonadotropin-releasing hormone antagonists in the management of patients with severe early-onset ovarian hyperstimulation syndrome

Objective. To study the efficacy of gonadotropin-releasing hormone (GnRH) antagonists in the treatment of patients with severe early-onset ovarian hyperstimulation syndrome (OHSS). Patients and methods. This study including 60 women was conducted between January 2021 and January 2023 at Al-Azhar University Maternity Hospitals and private ART centers. Approval from the Research Ethics Committee was obtained to conduct the study. Patients were randomly divided into two groups: group I (n = 30; control group) received only standard therapy for severe OHSS, group II (n = 30; study group) received standard therapy and cetrorelix. Results. The percentage of patients who required paracentesis, the mean serum creatinine level 48 hours after GnRH antagonist injection, and the percentage of patients who had persistent oliguria 48 hours after GnRH antagonist injection were significantly lower in the study group (cetrorelix group) compared with the control group. Patients in the cetrorelix group had a significantly shorter mean length of hospital stay and mean recovery time than patients in the control group. Conclusion. The therapeutic efficacy of the GnRH antagonist cetrorelix for the treatment of patients with severe early-onset OHSS was demonstrated. Key words: gonadotropin releasing-hormone antagonist; severe early-onset ovarian hyperstimulation syndrome

Nierenersatztherapie

The clinical indications for initiating acute renal replacement therapy (ARRT) include life-threatening refractory disturbances of electrolyte, acid-base and fluid balances as well as severe clinical symptoms of the uremic syndrome. In most other cases a watch and wait strategy is justified; however, a consistent (at least daily) re-evaluation is mandatory. In intensive care patients with persistent oliguria or anuria for > 72 h despite stable hemodynamics and adequate volume status, initiation of RRT should be considered even in the absence of urgent clinical indications. For continuous RRT the guidelines recommend a total effluent volume (dialysate plus filtrate) of 20–25 ml/kg body weight/h which usually requires a higher prescription of effluent volume. The treatment duration and frequency of intermittent RRT should primarily be tailored to the patients’ individual needs regarding fluid, electrolyte, and acid-base balances. Treatment sessions every 2 days will usually be sufficient to achieve adequate solute clearance. Basic prerequisites for attempts at weaning from ARRT are stable hemodynamics, adequate fluid, electrolyte, and acid-base statuses and a urine output of at least 500 ml/24 h or a positive response to a furosemide stress test. The successful recovery of kidney solute clearance can be demonstrated by performing an endogenous creatinine clearance or quantification of the kinetic estimated glomerular filtration rate (KeGFR).

Acute Kidney Injury and COVID-19: A Picture from an Intensive Care Unit

Introduction: Acute kidney injury (AKI) is a frequent complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care unit (ICU) for severe respiratory failure. The aim is to evaluate the rate of AKI, defined according to Kidney Disease: Improving Global Outcome guidelines, in a series of critical COVID-19 patients admitted to the ICU of a single tertiary teaching hospital. Methods: From April to May 2020, all consecutive critically ill COVID-19 patients admitted to the ICU who did not meet exclusion criteria (length of ICU stay <48 h, ESRD requiring dialysis, and patients still hospitalized in ICU at the time of data analysis) were enrolled in this study. Patients were stratified according to the highest AKI stage attained during ICU stay. Results: Sixty-one patients were included in the analysis. AKI was observed in 35/61 patients (57.4%): 25/35 episodes (71.4%) were observed within the first 7 days. AKI was classified as follows: 17.1% stage 1, 25.7% stage 2, and 57.2% stage 3. Fourteen out of 20 stage-3 patients required continuous renal replacement therapy (CRRT), mostly related to persistent oliguria. The overall ICU mortality was 68.9%, and it was higher in patients developing AKI if compared to no-AKI patients (p = 0.006). Renal function recovery of any grade was observed in 14 out of 35 AKI patients (40%). Among patients undergoing CRRT, 13 patients were still dialysis dependent at the time of death. Conclusion: In critical COVID-19 patients, ICU mortality is particularly high, especially in patients developing AKI. An accurate monitoring of renal function in early phases of respiratory failure should be ensured in order to timely apply any strategy aimed at limiting renal complications during ICU stay.

Rhabdomyolysis-induced acute kidney injury requiring hemodialysis after a prolonged immobilization at home in 2 morbidly obese women: case reports with literature review

BackgroundRhabdomyolysis may develop into acute kidney injury (AKI), a life-threatening complication. Obese people are at risk for rhabdomyolysis due to prolonged immobilization. However, there are only a few reports of rhabdomyolysis-induced AKI due to prolonged immobilization after falls in morbidly obese people. Myoglobin is a causative compound for rhabdomyolysis-induced AKI, but the lack of treatments targeting its mechanism is a problem.Case presentationTwo morbidly obese women (body mass index > 40.0 kg/m2) who fell on the floor at home and remained in the same posture for more than 12 h developed rhabdomyolysis-induced AKI. Both patients received aggressive fluid resuscitation but required hemodialysis because of persistent oliguria. They underwent 11 and 2 intermittent hemodialysis (HD) sessions with a conventional polymethylmethacrylate (PMMA) high-flux dialyzer, respectively, and their renal functions returned to baseline after withdrawal of HD.ConclusionsWe should be aware that morbidly obese people are at risk for rhabdomyolysis-induced AKI due to prolonged immobilization, such as after falls. At present, prophylactic renal replacement therapy (RRT) is not recommended for rhabdomyolysis. We need to reevaluate whether RRT using the appropriate membranes to effectively remove myoglobin including the PMMA membrane can improve the renal outcome in patients with rhabdomyolysis-induced AKI.

Prediction Efficiency of Postoperative Acute Kidney Injury in Acute Stanford Type A Aortic Dissection Patients with Renal Resistive Index and Semiquantitative Color Doppler.

Objectives This study is aimed to evaluate the efficiency in early prediction of postoperative persistent acute kidney injury (PAKI) after surgery in acute Stanford type A aortic dissection (AAAD) patients by using Doppler renal resistive index (RRI) and semiquantitative color (SQC) Doppler grade, respectively. Methods 84 AAAD patients received Sun's surgical management, and 67 patients were enrolled. RRI and SQC Doppler grade were evaluated by ultrasonography, respectively, at 6 hours after surgery. Serum creatinine (sCr) was recorded before operation and at 24 hours, 48 hours, and 72 hours after operation. AKI grade was evaluated according to the classifications of the Acute Kidney Injury Network (AKIN). PAKI is defined as persistent oliguria and/or sCr elevation after 3 days. RRI and SQC Doppler grade were compared, respectively, between the PAKI and non-PAKI groups. Potential predictors were first tested by univariate logistic regression analysis, and a multivariate model was identified to determine the independent predictive ability of RRI and SQC Doppler grade for the PAKI. Receiver operating characteristic (ROC) analysis was performed to compare the diagnostic accuracy between RRI and SQC Doppler grade in early prediction of PAKI by using AKIN classifications as the reference standard. Results Of a total of 67 patients enrolled during the study period, 21 (31.3%) patients suffered from PAKI and 8 (11.9%) patients required dialysis. There are significant differences in RRI (0.80 ± 0.09 vs. 0.70 ± 0.05, P=0.002) and SQC Doppler grade (x2=12.193, P=0.007) between the 2 groups with and without PAKI. Univariate analysis showed that RRI, SQC Doppler grade, length of stay in ICU, time of CPB, and length of stay in hospital were significant predictors of PAKI. RRI and the SQC Doppler grade remained independent predictors of PAKI. Area under the curve (AUC) of RRI was 0.855 (95% CI, 0.74–0.96) with cutoff value 0.725 (sensitivity 90.9% and specificity 71.1%), AUC of SQC Doppler grade was 0.642 (95% CI, 0.49–0.79) with cutoff value grade 2 (sensitivity 50% and specificity 73.3%). Conclusion Both postoperative RRI and SQC Doppler grade are independent predictors for PAKI after surgery in AAAD patients. Both postoperative RRI and SQC Doppler grade can be obtained rapidly by bedside ultrasound, which is a good tool for early prediction for postoperative PAKI.

A Study on Acute Kidney Injury in Intensive Care Setting

A Study on Acute Kidney Injury in Intensive Care Setting

Oliguria: an earlier and accurate biomarker of acute kidney injury?

In the context of the critically ill patient, the onset of consistent oliguria is an ominous sign that requires immediate attention. Without intervention, intermittent oliguria may turn into persistent oliguria or evolve to acute kidney injury (AKI), with severe associated morbidity and mortality. Whether the addition of urine output to the serum creatinine criteria permits earlier and more specific detection of AKI is controversial, but current evidence supports its importance in early diagnosis and management.

Factors associated with acute renal failure in children with rhabdomyolysis

Pigment nephropathy accounts for approximately 3% of all cases of acute renal failure (ARF) in children. Studies of risk factors associated with ARF and the need for renal replacement therapy (RRT) in children with rhabdomyolysis-associated pigment nephropathy consist of retrospective case series with variable inclusion criteria. Our objective was to evaluate clinical and laboratory characteristics, etiology, initial fluid therapy, prevalence of ARF and the requirement for RRT in pediatric patients with acute rhabdomyolysis. Twenty-eight patients (19 male) with a mean age of 11.1 +/- 5.6 years were studied. Acute renal failure occurred in 11 patients (39%), seven of whom (64%) required RRT. Features associated with the need for RRT included history of fever, persistent oliguria, admission blood urea nitrogen level, creatinine, Ca(2+), K(+), bicarbonate and aspartate aminotransferase. Most of these factors are related to the level of renal insufficiency and degree of muscle injury. There was no difference in admission and peak creatine kinase (CK) levels between those who did or did not require RRT. However, all who required RRT had a peak CK level > 5000 U/L.

Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings

BackgroundHornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis.Case presentationWe describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis). He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids.ConclusionRare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal function

Meta-analysis of frusemide to prevent or treat acute renal failure

Objective To investigate the potential beneficial and adverse effects of frusemide to prevent or treat acute renal failure in adults.Design Meta-analysis of randomised controlled trials.Data sources Cochrane controlled trials register...

Pathogenesis of acute renal failure associated with the HELLP syndrome: a case report and review of the literature

Acute renal failure is a rare but serious complication of pregnancy. We describe a 31-year-old woman with haemolytic anemia, elevated liver enzymes, low platelets (HELLP syndrome) who developed acute peripartum renal failure. Renal biopsy performed 2 weeks later because of persistent oliguria revealed thrombotic microangiopathy and acute tubular necrosis. This case highlights the probable pathogenesis of acute renal failure in HELLP patients and explains why it resolves in the majority of cases. A review of the literature that describes renal histology in HELLP patients is presented.

The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy.

The healthy term, and particularly the premature infant, is born with a very low glomerular filtration rate (GFR), controlled by a delicate balance of intrarenal vasoconstrictor and vasodilator forces. Vasoactive disturbances can easily further reduce the already low GFR. The newborn infant is thus prone to develop vasomotor nephropathy (VMNP) or acute renal failure (ARF). The main causes for ARF at this young age are prerenal mechanisms, and include hypotension, hypovolemia, hypoxemia perinatal asphyxia, and neonatal septicemia. Other causes include the administration of angiotensin converting enzyme inhibitors, indomethacin and tolazoline. The most-important factors governing the ultimate renal prognosis are the severity of the underlying disorder, the rapidity of an accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic complications. The immediate treatment is of particular importance in VMNP, i.e., prerenal ischemic ARF, and consists of correcting abnormalities in fluid homeostasis and reduction of the complications of the acute azotemic state (uremia, hyperkalemia, acidosis, and hypertension). In severe and prolonged (established) ARF, temporary dialysis therapy may be indicated. Prerenal ARF with oliguria or anuria warrants immediate volume resuscitation. Special attention should be given to infants with congestive heart failure (CHF). The sick neonate with persistent oliguria and CHF should be treated with intravenous dopamine. Furosemide (FM) is the second line of therapy for babies with indomethacin-induced ARF. In most other conditions, the therapeutic effect of FM is limited to a transient increase in urine flow, without improving basic renal function. The special conditions of the maturing kidney have to be appreciated in order to protect babies from undue renal injury. With the increasing knowledge of the mechanisms governing the development of ARF, progress has been made in the development of new treatment modalities. For example theophylline, calcium antagonists, ATP-MgCl2, thyroxine, and a variety of cytokines may in the near future be used to prevent or ameliorate VMNP and/or recently established ARF. With a combination of time-honored and new therapeutic strategies, there may well be a brighter future for neonates with vasomotor, prerenal, ischemic ARF.

TRAUMATIC RHABDOMYLOYSIS FROM SEVERE BEATING—EXPERIENCE OF VOLUME DIURESIS IN 200 PATIENTS

Fluid loading with balanced salt solution (BSS) was carried out in 200 patients with extensive soft tissue injuries from severe beatings. Urinary volume and dipstick specific gravity testing were used to monitor renal function with administration of furosemide for persistent oliguria. Acute intrinsic renal failure (AIRF) occurred in 21 patients (10.5%) and five patients died (2.5%); two of hyperkalemia, two of sepsis and one of multiple organ failure. Significantly increased rates of AIRF and death were associated with injury-admission intervals of more than 12 hours, severe metabolic acidosis, low initial hemoglobin, heavy pigmenturia, and high serum creatine kinase (CK) levels. An increased serum creatinine/BUN ratio was noted in four of the five patients who died. An average of 7.5 L fluids was needed in non-AIRF patients to achieve adequate diuresis with a mean positive fluid balance of 4.7 L. No patient without pigmenturia developed AIRF. Balanced salt solution volume diuresis supplemented with furosemide as necessary appears to be safe and effective in preventing AIRF in soft tissue injuries sustained in beatings.

Birth asphyxia associated oliguria: Relationship to outcome at 1 year

The relationship between the degree of oliguria following severe birth asphyxia and outcome at 12 months was examined in 31 infants. All 31 infants developed encephalopathy following severe birth asphyxia and 25 had oliguria for 24 h or more following delivery. Eighteen had persistent oliguria (i.e. greater than 48 h) and the remaining seven had transient oliguria (between 24 and 48 h). Poor outcome (death or neurological abnormality at 12 months) was significantly associated with the degree of oliguria. Encephalopathy, however, was found to be more closely correlated with poor outcome rather than duration of oliguria and a stepwise regression model confirmed that encephalopathy was the more powerful predictor of poor outcome. In those situations where an infant's degree of encephalopathy can not be assessed accurately (e.g. muscle relaxant use) the duration of oliguria may prove a useful prognostic indicator.

Low dose dopamine in the treatment of persistent oliguria in pre-eclampsia

Oliguria in pre-eclamptic women is most often a result of decreased intravascular volume. In a small number of patients, renal vascular spasm may be the cause of decreased urine output. Prolonged oliguria/anuria secondary to vasospasm may lead to permanent renal damage. When volume repletion is unsuccessful in restoring urine output, some authors have suggested the use of peripheral vasodilators such as hydralazine. Dopamine in low doses 2 μg/kg per min was used successfully to restore urine output within an hour in a pre-eclamptic patient who had been essentially anuric for 8 h. Volume administration and hydralazine were unsuccessful. In the rare instance of a patient who is unresponsive to conventional methods, low dose dopamine may provide an adjunctive therapy to restore urine output after delivery. Central monitoring is essential in following such patients.

Utilisation de la noradrénaline dans le traitement du choc septique

The effects of noradrenaline were studied in 16 patients, with either a hyperkinetic septic shock syndrome or a septic shock resistant to dobutamine treatment. The study aimed to restore normal tissue perfusion pressure, assessed by a return to normal of urine output or blood pressure. An optimal left ventricular filling pressure, estimated by the pulmonary capillary wedge pressure, was obtained for each patient using a Swan-Ganz catheter. The administration of 10.6 ± 0.5 μg · kg −1 · min −1 dobutamine (starting dose : 6 μg · kg −1 · min −1) was started when the cardiac index (CI) was less than 3.31 · min −1 · m −2 after vascular filling with plasma expanders. Patients became eligible for noradrenaline treatment when they fulfilled the following conditions : arterial systolic pressure (Pa sys) ⩽ 90 mmHg ; systemic vascular resistances ⩽ 600 dyn · s · cm −5 ; CI ⩾ 3.5 l · min −1 · m −2 ; persistent oliguria (< 30 ml · h −1). This drug was given at a constant rate with a starting dose of 0.5 μg · kg −1 · min −1, increased every 10 min by 0.3 to 0.6 μg · kg −1 · min −1 according to the effects on Pa sys and hourly urine output. Eight patients received noradrenaline alone ; the efficient dose was 0.9 ± 0.2 μg · kg −1 · min −1, and it was used for a mean 5.1 ± 1 days. CI increased in those patients who were given both noradrenaline and dobutamine. Thirteen out of the 16 patients had a dramatic increase in urine output ; only three patients remained oliguric. There were no effects on serum creatinine concentration, anion gap, intrapulmonary shunt and oxygen consumption. Sixty nine percent of the patients survived the episode of septic shock and 50 % were discharged from hospital. The use of noradrenaline with or without dobutamine in the treatment of septic shock is recommended.

Renal injury in the asphyxiated newborn infant: Relationship to neurologic outcome

The relationship of renal and central nervous system injury was prospectively evaluated in 120 asphyxiated infants. Renal evaluation findings were considered abnormal if there was oliguria (urine output less than 1 ml/kg/hr), which was designated transient if present in the first 24 hours only and persistent if present for at least 36 hours, or if the urinary beta 2-microglobulin concentration from first-void urine was elevated: (1) Thirteen infants had persistent oliguria; the urinary beta 2-microglobulin level was elevated in all. The six term infants had clinical signs consistent with hypoxic-ischemic encephalopathy (HIE); all six had ultrasonographic abnormalities. The outcome was poor (i.e., death or long-term neurologic deficits) in five of six infants. The seven preterm infants with persistent oliguria had clinical evidence of HIE, and three infants had intraventricular hemorrhage; all seven infants died. (2) Fifteen infants had transient oliguria (beta 2-microglobulin level was elevated in eight infants). Two of the eight term infants had evidence for HIE; the cranial ultrasound scan was normal in all. At follow-up, seven term infants are normal and one is abnormal. Six of the seven preterm infants with transient oliguria had clinical evidence of HIE; three infants had intraventricular hemorrhage. Three infants died, and the four survivors are normal at follow-up. (3) Ninety-two infants had normal urine output. Of the 22 term infants, two developed signs of HIE, and the ultrasound scan was abnormal in three infants. Of the 70 preterm infants, eight (11%) had clinical signs consistent with HIE, the ultrasound scan was abnormal in 20 of 64 (31%) infants scanned, and 14 (20%) infants died. Most of the followed infants are normal. Thus oliguria was significantly associated with clinical signs of HIE, including seizures, death (specifically in the premature infant), and long-term neurologic deficits. These data suggest that oliguria in the perinatal period is a sensitive indicator of infants at risk for long-term neurologic deficits.

Paralysis, Rhabdomyolysis and Haemolysis Caused by Bites of Russell's Viper (&lt;italic&gt;Vipera russelli pulchella&lt;/italic&gt;) in Sri Lanka: Failure of Indian (Haffkine) Antivenom

In Sri Lanka, Russell's viper, Vipera russelli pulchella, kills more people than any other species of snake. At Anuradhapura in the dry central zone of the island we studied 23 patients with systemic envenoming after proven bites. Seventy-three per cent had swelling at the bite site. Neurotoxicity was the commonest sign of systemic envenoming: 82 per cent had external ophthalmoplegia and 77 per cent had ptosis. Incoagulable blood was found in 59 per cent but only 36 per cent had spontaneous bleeding. Other signs included generalized muscle tenderness (32 per cent), black urine (27 per cent) and persistent oliguria (9 per cent). Laboratory studies showed evidence of a severe clotting disorder: fibrinogen was often depleted as were factors V and X. Fibrin degradation products, including cross-linked moieties, were grossly elevated, clear evidence for enhanced fibrinolysis. Intravascular haemolysis, unrelated to G6PD deficiency, was often present. Myoglobin was detected in the plasma of all 19 patients tested (range 100- greater than 8000 ng/ml) and in the urine in 14 of 18 patients (110- greater than 16,000 ng/ml). Venom antigen (16.5-702 ng/ml) was detected by specific ELISA in the serum of all patients. Its concentration fell with the administration of 50-200 ml of Haffkine polyspecific antivenom raised against Indian venoms. Complete permanent clearance of venom antigen from the circulation was seen in only one of 21 patients who were followed until discharge. Blood coagulability was restored between one and 25 h (mean 8.8) after the first dose of antivenom in the 12 surviving patients whose clotting defect could be followed; no dramatic reversal of neuromyotoxic signs was seen. Haffkine antivenom thus has limited efficacy against systemic poisoning by Russell's viper in Sri Lanka.

Clinical indications for pulmonary artery catheterization in the patient with severe preeclampsia

The obstetric literature reflects an increased interest in invasive hemodynamic monitoring during the past decade. While much of this interest has focused on research applications, the patient with severe preeclampsia may benefit clinically from pulmonary artery catheterization under several circumstances. These conditions include severe hypertension unresponsive to conventional antihypertensive therapy, pulmonary edema, persistent oliguria unresponsive to fluid challenge, and in induction of conduction anesthesia in select patients. Theoretical and clinical evidence to support this contention is presented.