During hemodialysis, small molecules are cleared from the blood by diffusion across a semipermeable membrane down a concentration gradient from blood into dialysate. The clearance of a substance depends on its molecular weight, the membrane surface area and type, as well as on blood and dialysate flow rates [6, 7]. Newer high-flux membranes can also remove high-molecular weight substances. Increasing blood and dialysate flow rates can increase the concentration gradient between blood and dialysate, thus increasing the rate of diffusion and elimination. Intermittent hemodialysis typically uses a blood flow rate of 200–500 mL/min and a dialysate flow rate of 500–1,000 mL/min [7, 8]. When a high-flux, high-efficiency membrane is used, a urea clearance exceeding 200 mL/min can be reached [9]. Hemodialysis is therefore the most efficient technique in terms of clearance. The major drawback is the risk of rebound toxicity due to redistribution of the toxin after stopping the treatment. In addition, hemodynamically unstable patients generally do not tolerate the high blood flows used in intermittent hemodialysis.

Sustained low efficiency dialysis (SLED) or prolonged intermittent renal replacement therapy (PIRRT) is a diffusive technique comparable to hemodialysis. In contrast, SLED is used continuously with lower rates of blood and dialysate flow than intermittent hemodialysis, typically 200 and 100 mL/min, respectively [10]. With these settings, a urea clearance of 70–80 mL/min can be reached [11]. Therefore, SLED is less efficient in removing toxic substances than hemodialysis. However, since flow rates are lower and treatment duration is longer, it is better tolerated by hemodynamically unstable patients and the risk of rebound toxicity is diminished.

Continuous venovenous hemodialysis (CVVHD) is another technique based on diffusion. However, blood flow and dialysis flow used are much lower than during SLED, typically 100–200 mL/min and 10–30 mL/min, respectively [5]. Current international guidelines recommend delivering an effluent volume of 20–25 mL/kg/h (www.​KDIGO.​com). Therefore, urea clearance is low (20–30 mL/min), which makes the technique unsuitable for the treatment of intoxications.

During hemofiltration, plasma ultrafiltrate is produced under influence of a pressure gradient across the hemofiltration membrane. Molecules up to 40 kDa can thus be cleared from the blood convectively. The plasma ultrafiltrate is replaced by a buffered replacement fluid, infused either before (predilution) or after the filter (postdilution). In postdilutional hemofiltration, clearance equals the ultrafiltration rate, typically ranging from 10 to 30 mL/min, with 20–25 mL/kg/h being the current recommendation for renal replacement therapy. When using high-volume hemofiltration, a clearance up to 85 mL/min can be reached, which makes the efficiency of this technique equal to SLED [5]. However, for small water-soluble molecules, extracorporeal removal by hemodialysis is much more efficient.

In continuous venovenous hemodiafiltration (CVVHDF), a dialysis component is added to conventional hemofiltration, by means of which the clearance can be increased [5]. However, the efficiency of this technique is insufficient for the treatment of intoxications.

During hemoperfusion, the blood passes through a cartridge containing a sorbent material. In order to be able to be removed by hemoperfusion, the toxic substance must have binding affinity to the sorbent in the cartridge and a low volume of distribution (Table 19.2). Despite their efficacy, the use of hemoperfusion cartridges has declined over the last 20 years due to limitations of their indications and shelf life [7, 12, 13].

The physicochemical and pharmacokinetic properties of barbiturates determine their suitability for extracorporeal elimination [15]. Their protein binding ranges from 5 % for barbital to 70 % for secobarbital, and their endogenous clearance ranges from 3 mL/min for barbital to 53 mL/min for secobarbital. Although for all barbiturates extracorporeal clearance is higher than endogenous clearance, barbital, phenobarbital, and secobarbital are most suitable for this technique because of their low endogenous clearance [15]. The choice for extracorporeal treatment in case of barbiturate overdose depends on the severity of the toxicity rather than on the serum level and should be considered in cases of severe hypotension, respiratory depression, or deep and prolonged coma. Until recently, hemoperfusion was the treatment of choice. However, with the use of high-flux, high-efficiency membranes, similar or even better elimination can be obtained with hemodialysis [16, 17].

Lithium is widely used in the treatment of bipolar affective disorders. It has a molecular weight of 74 Da, a distribution volume of 0.6–0.9 L/kg body weight, and it is not protein bound, which makes it an ideal substance to be removed by renal replacement therapy. With hemodialysis, an extraction ratio of 90 % and a clearance ranging from 63 to 114 mL/min can be achieved [18]. Hemodialysis is even more effective in removing lithium than the kidney itself, since 70–80 % of lithium filtered by the kidney is reabsorbed in the proximal tubule. Hemodialysis should be started in case of confusion, stupor, coma, or seizures. Although the serum lithium level is effectively lowered by hemodialysis, a rebound rise in serum levels occurs 6–8 h after cessation of the treatment, since lithium redistributes to the circulation from the interstitial space [19]. Therefore, hemodialysis should be continued until the serum lithium level remains below 1 mEq/L.

The biguanide metformin is the most widely used oral antidiabetic agent in the world. Yet it carries the risk of metformin associated lactic acidosis (MALA), which usually occurs in cases of overdose or renal failure. Although rare, MALA carries a mortality risk of 50 % [20]. Metformin has a molecular weight of 166 Da, is not protein bound, and is excreted by the kidney by means of glomerular filtration and tubular secretion. Its renal clearance therefore exceeds the creatinine clearance and ranges from 552 to 642 mL/min, reaching a plasma elimination half-life of 1.5–4.7 h [21]. Metformin intoxication itself can induce acute renal failure, which aggravates toxicity. By means of hemodialysis, metformin can be removed with clearances up to 170 mL/min [22]. Extracorporeal treatment should be performed in cases of refractory lactic acidosis or impaired renal function [23–25].

At therapeutic levels, salicylates have over 90 % protein binding, which decreases to 50–75 % at toxic levels, due to saturation. Salicylates are metabolized in the liver and excreted by the kidney. The elimination half-life is dose dependent, ranging from 2 h at a low dose to 30 h at a high dose. Treatment with hemodialysis should be started when the serum level exceeds 700 mg/L or when the clinical situation deteriorates (altered mental status, respiratory failure, pulmonary edema, severe acid-base disturbances, renal failure) [26]. Hemodialysis is recommended as the extracorporeal treatment of choice, since it more rapidly corrects metabolic acidosis and electrolyte disturbances [27].