Not just a result of excessive ultrafiltration, hemodynamic instability related to renal replacement therapy (HIRRT) can result from multiple, independent, and potentially overlapping mechanisms through which RRT results in decreased cardiac output or decreased peripheral resistance. An improved understanding of these mechanisms may lead to better interventions to limit HIRRT across all RRT modalities commonly used in the ICU. |
Introduction
Intervention | Potential mechanism(s) | Supporting evidence | Additional comments |
---|---|---|---|
Limit UF rate Reduce UF goal Lengthen treatment time | Allows for adequate plasma refilling to replace intravascular fluid removed by UF and thereby prevents intravascular hypovolemia. | Hemodynamic benefits of CRRT/SLED vs IHD are presumed but high-level evidence from comparative trials is lacking (as they may not be feasible/safe) | Reducing fluid removal goals may result in greater fluid overload which is associated with increased mortality. More healthcare resources needed if more dialysis time is required. HIRRT is common across RRT modalities (including CRRT) |
‘Slower’ RRT modality (i.e., SLED/CRRT) (lower QB, lower QD, increased treatment time) | Less osmotic shift and decreased UF rate: increased plasma refilling and less intravascular hypovolemia | As above | No clear evidence regarding benefit of ‘slower’ RRT modalities on mortality, renal recovery |
Isolated UF (i.e., pure ultrafiltration with no dialysis component) | No osmotic shift, increased plasma refilling | Hemodynamic stability of UF without diffusive clearance vs HD | Isolated UF allows for fluid removal but not solute clearance. [It involves only convective clearance (through solute drag) if dilutional fluid is added. There is no diffusive clearance which is much more efficient in clearing small molecules] |
Hypertonic infusions (hypertonic saline, mannitol, albumin) | Less osmotic shift, increased oncotic pressure prevents intravascular hypovolemia | Higher pre-HD plasma osmolality and hypoalbuminemia associated with increased risk of HIRRT; lack of evidence for albumin infusion | In critically ill patients, the effective crystalloid:colloid ratio is lower than expected. In septic patients with leaky capillaries, albumin (or mannitol) may be less likely to remain in the intravascular space to exert an osmotic or oncotic effect |
Higher dialysate Na+ and Na+ profiling | Less osmotic shift; less intravascular hypovolemia | Hemodynamic benefit in critically ill patients has mixed results | May result in positive sodium balance which correlates with greater interdialytic weight gain in maintenance HD. Unclear if this is relevant to the AKI/critically ill patient population |
Lower dialysate temperature | Promotes vasoconstriction, increases SVR, limits myocardial stunning | Hemodynamic benefit in ESKD patients on maintenance HD and cardioprotection: reduced LV mass, preserved LV function | Strong evidence that it improves hemodynamic stability in maintenance hemodialysis patients. Limits intradialytic myocardial stunning in this population. Studies show that myocardial stunning also occurs in critically ill patients on HD and CRRT |
Relatively higher dialysate Ca2+ Lower serum to dialysate Ca2+ gradient | Increased myocardial contractility, decreased arrhythmia risk, increased vascular tone | Improved hemodynamic tolerance; increased risk of cardiac arrest with lower dialysate Ca2+; increased mortality with hypoCa2+ in critically ill AKI | Less intradialytic hypotension in maintenance hemodialysis patients. Potential harms related to positive calcium balance in this population. Risks/benefits unclear in critically ill patients |
Bicarbonate buffer (versus lactate) | Does not cause lactic acidosis. Acidosis may lead to vasoplegia, less responsiveness to vasopressors | Less HIRRT (and acidosis) with bicarbonate buffer vs lactate buffer | Lactate accumulation occurs with lactate buffer when liver dysfunction prevents the usual rapid conversion of lactate to bicarbonate |
Bio-compatible dialyzer membranes | Minimize complement activation and inflammatory response | Unmodified cellulose (cuprophane) associated with worse outcomes | Bio-compatible dialyzer membranes are standard in current practice |
Inclusion of convective clearance (hemofiltration); HVHF | Improved clearance of higher molecular weight pro-inflammatory solutes may reduce inflammation and thereby reduce vasodilation, myocardial stunning | Mixed evidence for hemodynamic benefit or improved mortality; HVHF not shown to be beneficial in septic AKI | Removal of high molecular weight anti-inflammatory factors also occurs with HVHF and might negate any potential benefits in sepsis/septic AKI |
RRT-related mechanisms for HIRRT
Excessive ultrafiltration
Rapid osmotic/oncotic shifts
Dialysis blood flow (QB)
Myocardial stunning
Effect of temperature changes with RRT
Dialysate/RRT fluid composition
Calcium concentration
Potassium concentration
Buffer
Dialyzer bio-incompatibility
Endotoxemia
Diffusive versus convective clearance modes
Clearance of vasopressors
Multimodal approach to the prevention of HIRRT
Study | Design | Intervention(s) | Occurrence of HIRRT | Significance |
---|---|---|---|---|
Intermittent hemodialysis | ||||
Lynch [82] | Retrospective cohort N = 191 patients; 892 sessions | Dialysate sodium profiling | Case: 36/242 = 14.9% Control: 59/650 = 9.1% | NS |
du Cheyron [83] | RCT N = 74 patients; 574 sessions | Blood volume and temperature control | BVM: 33/190 = 17.4% BVM + BTM: 30/194 = 15.5% Control: 32/188 = 17.0% | NS |
du Cheyron et al. [57] | Prospective cohort N = 62 patients; 572 sessions | Blood volume and temperature control | Case: 41/189 = 21.7% Control: 110/383 = 28.7% | P = 0.09 |
Schortgen et al. [5] | Retrospective cohort N = 121 patients; 537 sessions | Multimodal approach | Case: 176/289 = 60.9% Control: 176/248 = 71.0% | P = 0.015 |
Paganini et al. [34] | Randomized cross-over study N = 10 patients; 60 sessions | Variable dialysate sodium and UF profiling | Case: 16.0% Control: 45.5% | Not reported |
Jardin et al. [41] | Prospective cohort N = 8 patients; 53 sessions | 17.5% albumin priming vs saline | Albumin: stable MAP and more UF (530 mL/h vs 366 mL/h) | MAP: P < 0.001 Not reported for UF |
Sustained low-efficiency dialysis | ||||
Edrees et al. [58] | Randomized cross-over study N = 21 patients; 78 sessions | Lower dialysate temperature (35 °C vs 37 °C) | Case: 0.7 ± 0.7 Control: 1.5 ± 1.1 | P < 0.0001 |
Albino [84] | RCT N = 75 patients; 195 sessions | Duration of RRT: 6 h vs 10 h | 6 h: 63/100 = 63.0% 10 h: 53/95 = 55.8% | NS |
Lima et al. [33] | RCT N = 39 patients; 62 sessions | Lower dialysate temperature with dialysate sodium and UF profiling | Case: 8/34 = 23.5% Control: 16/28 = 57.1% | P = 0.009 |
Continuous renal replacement therapy | ||||
Robert et al. [60] | Randomized cross-over study N = 30 patients | Lower heating device temperature (36 °C vs 38 °C) | Less interventions for HIRRT with cooler temperature | P = 0.08 |
Eastwood et al. [46] | Prospective cohort N = 21 patients; 41 RRT starts | CRRT pump speed | No HIRRT reported at CRRT initiation | Not applicable |
Rokyta et al. [59] | Prospective cohort N = 9 patients | CRRT-induced cooling (SF and RB warmed to 37 °C vs no warming) | MAP and SVR increased with cooling | P < 0.05 |
RRT-related factor | Suggestion | Rationale | Comment |
---|---|---|---|
Ultrafiltration (fluid removal) rate | Set fluid removal goals to avoid/reduce net positive fluid balance. Check for preload dependence when HIRRT occurs and only reduce ultrafiltration goals if preload dependence is present | HIRRT has many causes beyond just excessive ultrafiltration. As a result, reduction of the ultrafiltration goal is not always the appropriate response to HIRRT (especially for patients with worsening fluid overload) | Starting (or increasing the dose of) a vasopressor or inotrope may be a more appropriate strategy to manage HIRRT when it is unrelated to excessive ultrafiltration |
Treatment time | Lengthen treatment times for intermittent RRT modalities if fluid removal is required For example, for intermittent HD, use a minimum 4 h treatment time; for SLED, consider extending usual treatment time | Longer treatment times enable lower ultrafiltration rates to achieve the same ultrafiltration goal. As such, they are more likely to allow for sufficient plasma refilling to prevent HIRRT | For intermittent HD, do not extend treatment time beyond 4–5 h if using conventional dialysate and blood flow rates (may result in dialysis disequilibrium due to overly effective solute clearance) For SLED, consider back-to-back sessions to achieve fluid removal goals if machine software does not allow for treatment time extension |
Dose (flow rates) | Start with moderate small solute clearance, especially in patients with significant uremia (hyperosmolality) For example, for intermittent HD, QB ≤ 200 mL/min and QD ≤ 300 mL/min; for CRRT, total effluent rate 20–25 mL/kg/h | More gradual reduction in plasma osmolality induce less fluid shift and promote plasma refilling | Ensure adequate RRT dose once osmolality/uremia has decreased Blood flow rate does not impact small solute clearance in CRRT (more dependent on total effluent rate). Therefore, one should not reduce QB in CRRT to less than usual (~ 150 to 200 mL/min) as clotting risk will increase and no reduction in HIRRT will be achieved |
Dialysate sodium concentration | Use higher dialysate sodium concentration for intermittent therapies (HD and SLED): e.g., ≥ 145 mmol/L | Reduced osmolar shift allows for more plasma refilling to occur | Do not employ this strategy in patients with hyponatremia due to risk of overly rapid correction if higher sodium dialysate solutions are used |
Dialysate calcium concentration | Consider using higher dialysate calcium concentration (e.g., 1.5 or 1.75 mmol/L) for intermittent therapies (HD and SLED) | Activating calcium-sensing receptors on vascular smooth muscle cells increases vascular tone Higher calcium potentiates cardiac contractility | Some studies have shown that using calcium to correct hypocalcemia in critically ill patients (not requiring RRT) may be harmful. The safety of routinely using higher dialysate calcium concentration in critically ill patients has not been studied |
Dialysate temperature | Use cool dialysate for intermittent HD or SLED: i.e., 0.5 °C less than the patient’s temperature (down to a minimum of 35.0–35.5 °C) | Cooling promotes peripheral vasoconstriction and increases blood volume return Also reduces myocardial stunning (presumably leading to improved cardiac output) | Most intermittent HD machines’ software does not allow for dialysate temperature settings < 35.0–35.5 °C (and the safety of using lower temperatures than this has not been studied) Less evidence exists regarding the impact of cooling patients using CRRT as compared to that supporting the use of cool dialysate in SLED and intermittent HD |
Buffer | Use a bicarbonate-based buffer (versus lactate-based) | Lactate-based buffers associated with more HIRRT | Acetate-based buffers are no longer used due to increased risk of HIRRT |