Viola Van Gorp

Renal and neurological side effects of colistin in critically ill patients

Colistin is a complex polypeptide antibiotic composed mainly of colistin A and B. It was abandoned from clinical use in the 1970s because of significant renal and, to a lesser extent, neurological toxicity. Actually, colistin is increasingly put forward as salvage or even first-line treatment for severe multidrug-resistant, Gram-negative bacterial infections, particularly in the intensive care setting. We reviewed the most recent literature on colistin treatment, focusing on efficacy and toxicity issues. The method used for literature search was based on a PubMed retrieval using very precise criteria.Despite large variations in dose and duration, colistin treatment produces relatively high clinical cure rates. Colistin is potentially nephrotoxic but currently used criteria tend to overestimate the incidence of kidney injury. Nephrotoxicity independently predicts fewer cures of infection and increased mortality. Total cumulative colistin dose is associated with kidney damage, suggesting that shortening of treatment duration could decrease the incidence of nephrotoxicity. Factors that may enhance colistin nephrotoxicity (i.e., shock, hypoalbuminemia, concomitant use of potentially nephrotoxic drugs) must be combated or controlled. Neurotoxicity does not seem to be a major issue during colistin treatment. A better knowledge of colistin pharmacokinetics in critically ill patients is imperative for obtaining colistin dosing regimens that ensure maximal antibacterial activity at minimal toxicity.

Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review.

In recent years, after all the attention has been focused on the dose for continuous renal replacement therapy (CRRT) in sepsis and systemic inflammation response syndrome (SIRS), the relatively negative results of all those studies did urge our expectations on new approaches regarding CRRT in sepsis and SIRS. So far, after the failure of the major randomized studies on dose, attention is now drawn to new membranes that could better eliminate massive amounts of unbound mediators in wider spectrum and also in greater magnitude Nevertheless, for septic acute kidney injury, the recommended dose will remain 35 ml/kg/h until the IVOIRE (hIgh VOlume in Intensive Care) study will be published. In this new armamentarium, we have distinguished the first tools that can still be called membranes ranging from AN69 Surface Treated (ST), SEPTEX, polymethylmetacrylate, to Oxiris that can still run with a CRRT device. Polymyxin B is still a kind of membrane although it has a larger surface, but it can run in a hemoperfusion system and is also much more selective. Adsorptive columns and sorbents are not anymore membranes but are seen as cartridges as the surface is extremely huge when compared with that of membranes (more than 500 m2). They can still run in a hemoperfusion device. At the very end, we do have apheresis or selective plasma exchange (also very close to sorbents and columns) but we have very few data up to now regarding sepsis. Regarding spectrum, CytoSorb seems to be very promising although it is not able to capture endotoxin and IL-10. Oxiris is also promising as it can capture endotoxin and cytokines. AN69 ST is very powerful to capture numerous cytokines and especially high-mobility group box 1 protein (a very upstream cytokine). Polymethylmetacrylate has also the power to capture endotoxin and numerous other cytokines probably with a larger magnitude than Oxiris although this is not proven. Lastly, high-porosity membranes (Septex) may play a role especially when used in continuous venovenous hemodialysis mode. At the end, if we look for a more enlarged spectrum and a higher magnitude, CytoSorb might be seen as the most promising although not having the ability to fix endotoxin. Future studies will tell us which membrane or sorbent will be most useful in the adjunctive treatment for sepsis.

Prevention and treatment of sepsis-induced acute kidney injury: an update

Sepsis-induced acute kidney injury (SAKI) remains an important challenge in critical care medicine. We reviewed current available evidence on prevention and treatment of SAKI with focus on some recent advances and developments. Prevention of SAKI starts with early and ample fluid resuscitation preferentially with crystalloid solutions. Balanced crystalloids have no proven superior benefit. Renal function can be evaluated by measuring lactate clearance rate, renal Doppler, or central venous oxygenation monitoring. Assuring sufficiently high central venous oxygenation most optimally prevents SAKI, especially in the post-operative setting, whereas lactate clearance better assesses mortality risk when SAKI is present. Although the adverse effects of an excessive “kidney afterload” are increasingly recognized, there is actually no consensus regarding an optimal central venous pressure. Noradrenaline is the vasopressor of choice for preventing SAKI. Intra-abdominal hypertension, a potent trigger of AKI in post-operative and trauma patients, should not be neglected in sepsis. Early renal replacement therapy (RRT) is recommended in fluid-overloaded patients’ refractory to diuretics but compelling evidence about its usefulness is still lacking. Continuous RRT (CRRT) is advocated, though not sustained by convincing data, as the preferred modality in hemodynamically unstable SAKI. Diuretics should be avoided in the absence of hypervolemia. Antimicrobial dosing during CRRT needs to be thoroughly reconsidered to assure adequate infection control.

Acute respiratory muscle weakness and apnea in a critically ill patient induced by colistin neurotoxicity: key potential role of hemoadsorption elimination during continuous venovenous hemofiltration

We describe a patient with severe New Delhi metallo-β-lactamase-1 Escherichia coli infection who developed convulsions rapidly followed by acute respiratory muscle weakness and apnea while receiving intravenous colistin. Toxic levels of colistin were rapidly removed by hemofiltration and, more specifically, by hemoadsorption.

Nutritional and Metabolic Alterations during Continuous Renal Replacement Therapy

Adequate feeding of critically ill patients under continuous renal replacement therapy (CRRT) remains a challenging issue. We performed a systematic search of the literature published between 1992 and 2012 using the quorum guidelines regarding nutrition in intensive care unit patients treated with CRRT. Daily recommended energy requirements during CRRT are between 25 and 35 kcal/kg with carbohydrates and lipids accounting for 60-70% and 30-40% of calorie intake, respectively. Daily protein needs range from 1.5 to 1.8 g/kg. Indirect calorimetry corrected for CRRT-induced CO2 diversion should be used to more correctly match calorie intake to the real needs. This type of tool is not yet available but hopefully soon. Electrolyte deficit as well as overload have been described during CRRT but, in general, can be easily controlled. Although not strongly evidenced, consensus exists to supplement important micronutrients such as amino acids (glutamine), water-soluble vitamins and trace elements.

Biomarkers for early diagnosis of AKI in the ICU: ready for prime time use at the bedside?

Because of its still rising incidence and high mortality rate in intensive care unit (ICU) patients, early recognition of acute kidney injury (AKI) remains a critical issue. Surprisingly, effective biomarkers for early detection and hence appropriate and timely therapy of AKI have not yet entered the clinical arena. We performed a systematic search of the literature published between 1999 and 2011 on potential early biomarkers for acute renal failure/kidney injury in an at-risk adult and pediatric population following the Quorum Guidelines. Based on this review, recommendations for the clinical use of these biomarkers were proposed. In general, kidney biomarkers may aid to direct early aggressive treatment strategies for AKI thereby decreasing the associated high mortality. To date, however, sensitivity and specificity of individual biomarker assays are low and do not sustain their routine clinical use. “Kits” containing a combination of established biomarkers, in conjunction with measured glomerular filtration rate, may enhance diagnostic and prognostic accuracy in the future.

Ropivacaine 3.75 mg/mL, 5 mg/mL, or 7.5 mg/mL for Cervical Plexus Block During Carotid Endarterectomy

Objective To examine the effect of 225 mg (7.5 mg/mL), 150 mg (5 mg/mL), and 112.5 mg (3.75 mg/mL) ropivacaine on quality of cervical plexus block during carotid endarterectomy. Methods Patients (n = 93) scheduled for carotid endarterectomy were randomized to receive a cervical plexus block with deep infiltration of 10 mL and superficial infiltration of 20-mL volumes of ropivacaine 7.5, 5.0, or 3.75 mg/mL. Pain, coughing, hemodynamic consequences of the block, postoperative visual analog scores, and pain satisfaction index were recorded. If necessary, anesthesia supplements with aliquots of 3 mL lidocaine 1% were given during surgery. Results Incidences of coughing and hoarseness were similar in all groups. More local anesthetic infiltrations were required in the ropivacaine 3.75-mg/mL and 5-mg/mL groups. Postoperatively, no intragroup differences were observed. A trend toward better pain satisfaction was observed in the ropivacaine 7.5-mg/mL group. Conclusion The best quality of cervical plexus block associated with the smallest incidence of pain for patients undergoing carotid endarterectomy was obtained with 30 mL of 225 mg and 150 mg of ropivacaine, respectively.

Continuous renal replacement therapy allows higher colistin dosing without increasing toxicity

Abstract Polymyxins are ‘‘old’’ antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise of multi-resistant Gramnegative bacterial infections worldwide has revived interest in these ‘‘forgotten’’ agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the pro-drug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used for treatment of pneumonia and bacteremia in critically ill patients. During their ICU stay, many of these subjects will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e., a high loading dose, followed by a maintenance dose up to 4.5 million IU tid). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such ‘‘CRRT rescue’’ therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.

Con: Dialy- and continuous renal replacement (CRRT) trauma during renal replacement therapy: still under-recognized but on the way to better diagnostic understanding and prevention.

Dialy- and continuous renal replacement (CRRT) trauma are still un(der)recognized conditions that may be encountered during blood purification therapy. This particular form of trauma requires timely identification, a better understanding of pathophysiology and a definition of at-risk groups to prevent or correct any associated unwarranted effects. Among others, progress in the knowledge of antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) behaviour during CRRT to obtain more efficient antimicrobial therapy with less side-effects is one key example of limiting CRRT trauma. Optimal anticipation and prevention of CRRT trauma will preserve the safe use of CRRT in haemodynamically unstable critically ill patients with acute kidney injury (AKI), especially in septic patients who are at the greatest risk.

A rare cause of dyspnea due to chylothorax

We report the case of an 8-year-old boy who presented to the emergency department of another hospital and was referred to our pediatric intensive care unit with dyspnea and tachypnea of recent onset. The diagnosis of massive chylothorax with mediastinal shift was made on chest radiographs and CT scan. Initial investigations revealed no definite cause for the chylothorax. On later radiography and CT imaging with 3D surface rendering, a marked bone loss of the left ribs, clavicle, and shoulder joint was shown. The diagnosis of Gorham–Stout disease associated with chylothorax was suspected and histologically confirmed.