Review article: Renal support in critical illness

Purpose

This review provides a focused and comprehensive update on established and emerging evidence in acute renal replacement therapy (RRT) for critically ill patients with acute kidney injury (AKI).

Principal findings

There have been considerable technological innovations in the methods and techniques for provision of extracorporeal RRT in critical illness. These have greatly expanded our capability to provide both renal and non-renal life-sustaining organ support for critically ill patients. Recent data suggest earlier initiation of RRT in AKI may confer an advantage for survival and renal recovery. Two large trials have recently shown no added benefit to augmented RRT dose delivery in AKI. Observational data have also suggested that fluid accumulation in critically ill patients with AKI is associated with worse clinical outcome. However, several fundamental clinical questions remain to be answered, including issues regarding the time to ideally initiate/discontinue RRT, the role of high-volume hemofiltration or other blood purification techniques in sepsis, and extracorporeal support for combined liver-kidney failure. Extracorporeal support with RRT in sepsis, rhabdomyolysis, and liver failure are discussed, along with strategies for drug dosing and management of RRT in sodium disorders.

Conclusions

We anticipate that this field will continue to expand to promote research and innovation, hopefully for the benefit of sick critically ill patients.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Selective Targeting of Human Alloresponsive CD8+ Effector Memory T Cells Based on CD2 Expression

Costimulation blockade (CoB), specifically CD28/B7 inhibition with belatacept, is an emerging clinical replacement for calcineurin inhibitor‐based immunosuppression in allotransplantation. However, there is accumulating evidence that belatacept incompletely controls alloreactive T cells that lose CD28 expression during terminal differentiation. We have recently shown that the CD2‐specific fusion protein alefacept controls costimulation blockade‐resistant allograft rejection in nonhuman primates. Here, we have investigated the relationship between human alloreactive T cells, costimulation blockade sensitivity and CD2 expression to determine whether these findings warrant potential clinical translation. Using polychromatic flow cytometry, we found that CD8⁺ effector memory T cells are distinctly high CD2 and low CD28 expressors. Alloresponsive CD8⁺CD2^hiCD28^? T cells contained the highest proportion of cells with polyfunctional cytokine (IFNγ, TNF and IL‐2) and cytotoxic effector molecule (CD107a and granzyme B) expression capability. Treatment with belatacept in vitro incompletely attenuated allospecific proliferation, but alefacept inhibited belatacept‐resistant proliferation. These results suggest that highly alloreactive effector T cells exert their late stage functions without reliance on ongoing CD28/B7 costimulation. Their high CD2 expression increases their susceptibility to alefacept. These studies combined with in vivo nonhuman primate data provide a rationale for translation of an immunosuppression regimen pairing alefacept and belatacept to human renal transplantation.     

Reduction strategies through the anterolateral exposure for fixation of type B and C pilon fractures

The surgical management of pilon fractures has evolved over the last several years with treatment shifting from acute definitive fixation to delayed fixation. One of the driving forces behind this change was the high incidence of soft tissue complications in those patients with high-energy pilon fractures (Orthopaedic Trauma Association 43B and 43C) managed with acute stabilization. Meticulous soft tissue handling along with delayed definitive fixation based on the soft tissue envelope has decreased the short-term complications associated with treatment of these injuries. Anterolateral exposure to the distal tibial articular surface allows for adequate visualization of most fracture patterns, novel reduction strategies, and successful implant placements. This exposure is useful in certain Type C pilon fractures, anterior and anterolateral Type B pilon fractures, and some extra-articular distal tibial fractures. The anterolateral exposure is not suitable in fractures with medial comminution, medial crush, impaction at the medial shoulder of the joint, segmental medial malleolar injuries, or varus deformity at the time of injury. The exposure has the advantage of excellent visualization of the articular surface up to the medial shoulder of the plafond while avoiding dissection of the anteromedial tibial surface.     

Chronic myeloid leukemia within a year of kidney transplant with elevated alkaline phosphatase correlated with imatinib therapy

The incidence of certain malignancies is significantly higher after organ transplant. However, there are rare reports of chronic myeloid leukemia in the posttransplant setting. The average reported interval between a transplant and the diagnosis of chronic myeloid leukemia is 44 months (range, 10- 96 mo). We report 2 patients with chronic myeloid leukemia within 1 year of a kidney transplant, which is significantly shorter than those previously reported. Both patients were receiving mycophenolate mofetil and tacrolimus for immunosuppression. They were treated with imatinib for chronic myeloid leukemia, and both patients demonstrated an isolated elevation of serum alkaline phosphatase that was directly correlated with imatinib. Despite a potential interaction between the 2 drugs, blood levels of tacrolimus and imatinib were not elevated during the course of treatment. Isolated elevation of alkaline phosphatase in this particular setting has not been reported previously.     

Power Doppler sonography of breast cancer: does vascularity correlate with node status or lymphatic vascular invasion?

OBJECTIVE: The purpose of our study was to determine how breast cancer vascularity, as revealed by power Doppler sonography, correlates with lymph node involvement and lymphatic vascular invasion. MATERIALS AND METHODS: Breast sonograms obtained during a 2-year period were retrospectively reviewed. Patients who underwent power Doppler sonography of solid masses and had biopsy-proven carcinoma composed our study population. Power Doppler findings were categorized according to the presence or absence of vessels. Pathologic findings were reviewed for lymph node involvement and lymphatic vascular invasion. RESULTS: Of 176 patients with breast cancer, vessels were seen on power Doppler sonography in 128 (73%) and not seen in 48 (27%). Of 126 patients who underwent lymph node dissection, vessels were seen in 97 (77%) and not seen in 29 (23%). Lymph node involvement was seen in 42 (43%) of the 97 patients in whom vessels were seen and in three (10%) of the 29 in whom vessels were not seen. Of 150 patients examined for lymphatic vascular invasion, vessels were seen in 111 (74%) and not seen in 39 (26%). Lymphatic vascular invasion was seen in 47 (42%) of the 111 patients in whom vessels were seen and in five (13%) of the 39 in whom vessels were not seen. CONCLUSION: Tumor vascularity revealed by power Doppler sonography correlated strongly with detection of lymph node involvement and lymphatic vascular invasion, with sensitivities of 93% and 90%, respectively. However, the specificities were low, at 32% and 35%, respectively. More important, patients with breast cancer in whom vessels were not revealed by power Doppler sonography also were unlikely to have lymph node involvement and lymphatic vascular invasion: Negative predictive values were 90% and 87%, respectively.     

Limited role for IVUS in the endovascular repair of aortoiliac aneurysms.

BACKGROUND: To determine the need for routine versus selective intraoperative IVUS during endovascular aortoiliac aneurysm (AIA) repair. METHODS: One-hundred and eighty-eight endovascular AIA repairs performed over a 5-year period were reviewed and included in the study. Surgeon-made aorto-uni-femoral grafts (n=78) and industry-made bifurcated or tube grafts (n=110) were used. In the initial 51 cases IVUS was routinely performed. In the latter 137 cases IVUS was used selectively. In this group graft deformities suspected on completion angiography or pullback pressure measurements were treated with balloon dilatation and stenting. IVUS was then performed only in the presence of a persistent pressure gradient or inconclusive angiographic findings. RESULTS: In the initial 51 cases IVUS revealed 20 lesions of which 8 were not initially detected angiographically and which required further treatment. In the latter 137 cases IVUS was necessary in only 1 case, and guided the treatment of an angiographically undetectable lesion. There have been no late episodes of graft compression, kinking, or thrombosis in the selective IVUS group. CONCLUSIONS: The use of pullback pressure measurements with a low threshold for angioplasty and stenting, especially in unsupported grafts, followed by the selective use of IVUS decreases the overall requirement for IVUS and its associated costs.     

Increasing incidence of midterm and long-term complications after endovascular graft repair of abdominal aortic aneurysms: a note of caution based on a 9-year experience

OBJECTIVE: To analyze the late complications after endovascular graft repair of elective abdominal aortic aneurysms (AAAs) at the authors' institution since November 1992. SUMMARY BACKGROUND DATA: Recently, the use of endovascular grafts for the treatment of AAAs has increased dramatically. However, there is little midterm or long-term proof of their efficacy. METHODS: During the past 9 years, 239 endovascular graft repairs were performed for nonruptured AAAs, many (86%) in high-risk patients or in those with complex anatomy. The grafts used were Montefiore (n = 97), Ancure/EVT (n = 14), Vanguard (n = 16), Talent (n = 47), Excluder (n = 20), AneuRx (n = 29), and Zenith (n = 16). All but the AneuRx and Ancure repairs were performed as part of a U.S. phase 1 or phase 2 clinical trial under a Food and Drug Administration investigational device exemption. Procedural outcomes and follow-up results were prospectively recorded. RESULTS: The major complication and death rates within 30 days of endovascular graft repair were 17.6% and 8.5%, respectively. The technical success rate with complete AAA exclusion was 88.7%. During follow-up to 75 months (mean +/- standard deviation, 15.7 +/- 6.3 months), 53 patients (22%) died of unrelated causes. Two AAAs treated with endovascular grafts ruptured and were surgically repaired, with one death. Other late complications included type 1 endoleak (n = 7), aortoduodenal fistula (n = 2), graft thrombosis/stenosis (n = 7), limb separation or fabric tear with a subsequent type 3 endoleak (n = 1), and a persistent type 2 endoleak (n = 13). Secondary intervention or surgery was required in 23 patients (10%). These included deployment of a second graft (n = 4), open AAA repair (n = 5), coil embolization (n = 6), extraanatomic bypass (n = 4), and stent placement (n = 3). CONCLUSION: With longer follow-up, complications occurred with increasing frequency. Although most could be managed with some form of endovascular reintervention, some complications resulted in a high death rate. Although endovascular graft repair is less invasive and sometimes effective in the long term, it is often not a definitive procedure. These findings mandate long-term surveillance and prospective studies to prove the effectiveness of endovascular graft repair.     

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of S-fluorouracil (250 mg/m²/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of S-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 1.5 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy. Presented at the Eighty-Second Annual Meeting of the American Radium Society, London, England, April l–5, 2000.