Commonly used crystalloids and their composition:
\r\n\tThe chemistry of modern and ancient evaporites, and their parent waters, is reflected in the mineralogy and facies distribution remaining in the geologic record.
\r\n\r\n\t
\r\n\tEvaporites are important economically because of their mineralogy, their physical properties in-situ, and their behavior within the subsurface. Evaporites as seals or cap rocks control the reservoir geometry and producibility. Economically important evaporite minerals are common in nature, such as; Sylvite, also known as Potash, or potassium chloride. It is used as a fertilizer ingredient and is an important plant nutrient. Gypsum (calcium sulfate) is also an important evaporite mineral and is primarily used to make building materials such as drywall. Halite (sodium chloride) is what one normally thinks of as “salt” and has been an important commodity for millennia.
The number of Kidney transplants has increased in last decades for many advances in diagnostic and therapeutic reasons. Kidney transplantation results in superior life expectancy and better quality of life if compared to dialysis treatment for patients with end-stage renal failure. The success of graft survival after kidney transplantation is closely associated with early graft function based on intraoperative perfusion characteristics of the allograft and good urine output. Clinicians must carefully adjust intravascular volume and arterial blood pressure to effectively perfuse the graft, and the time course of volume expansion seems important for adequate hydration. The ultimate goal for any renal transplantation patient is to have an optimally functioning graft as early as possible after completion of surgery. Key strategies that are used to achieve this goal involve the optimal management of the intravascular volume and achievement of early urine output. One of the reasons for graft failure after renal transplantation is inadequate graft perfusion caused by mis-management of perioperative hydration policy.
\n\t\tKnowledge of the pathophysiologic consequences of chronic renal failure is too important for anesthesiologists, because many of these patients have at least one of these sequences, most commonly hypertension, coronary artery diseases, diabetes mellitus and pulmonary dysfunction. Additionally, disturbance in acid-base, electrolytes and fluid balance are usually related to a marked decline in the glomerular filtration rate (GFR) caused by a variety of systemic diseases such as diabetes mellitus or hypertension, and renal disorders as chronic glomerulonephritis,cystic kidney disorder,interstitial nephritis, obstructive uropathy, and lupus nephritis. It is essential to recognize the etiology, because the physician should control the problem and does not rely on the patients’ ability to comply with the treatment.
\n\t\tThe practice of anesthesia for kidney transplant requires a thorough understanding of the metabolic and systemic abnormalities in end stage renal disease, familiarity with transplant medicine and expertise in managing and optimizing these patients for the best possible outcome.
\n\t\t\tPatients undergoing renal transplant surgery possess several risk characteristics like cardiovascular diseases, hypertension, diabetes mellitus, and the problems of dialysis. Therefore a thorough pre-operative assessment is crucial for successful intra- and postoperative management. The preoperative work-up includes Past- medical history, dialysis evaluation (How long? How often? When was the last dialysis? ), serum electrolytes (serum potassium), ECG, chest X-ray and cardiac echocardiography. Dialysis is usually indicated within 24-48 hrs before the operation. Overzealous ultra filtration is best avoided. Volume status is roughly estimated by their dry weight. Decline of more than 2-4 kg during dialysis suggests significant intravascular depletion. Therefore it was advisable to restrict fluid removal during preoperative dialysis to a target of 1-2 kg above the formal dry weight. (Schnuelle and Johannes Van der Woude: 2006). Antihypertensive drugs and cardiovascular medications should be continued until the day of surgery.
\n\t\tThe primary goal of fluid administration is to ensure stable hemodynamics by rapidly restoration the circulating plasma volume. However, excessive fluid accumulation, particularly in the interstitial tissue should be avoided. The intra-operative hydration strategy of both kidney donor and recipient are of paramount important for the insurance the success of kidney transplantation and ensure good function of the graft after surgery.
\n\t\t\t\n\t\t\t\t\tOthman and his colleagues (2010) described in their study the hydration regimen of their living kidney donors. The kidney donors, in this study, had received 1500 mls normal saline and 1500 mls Ringer\'s lactate solution, supplemented by crystalloid titrated to match the urine output from the start of the surgery until the renal vessels were clamped. Kidney donors also received 40 mg furosemide and 150 mL mannitol 10% before nephrectomy.
\n\t\t\t\tTo maintain good diuresis, fluid administration for kidney donors is usually generous (10-20 ml/kg/hr) using isotonic crystalloids during the intra-operative time (Baxi et al 2009). However, some centers recommend overnight preoperative hydration with intravenous fluids and preloading the patients with colloids just before induction of anesthesia. Good hydration of the donor in addition of good hemodynamic intraoperative stability are essential requirements for the graft to tolerate ischemia time after nephrectomy with less harm till vascular anastomosis being completed.
\n\t\t\t\tIn our center, the harvested kidney in living kidney donor was usually submerged immediately in iced Ringer\'s lactate solution, and the renal artery was flushed with 250 to 300 mls cold Ringer\'s lactate solution (4°C) mixed with papaverine 120 mg, heparin 5000 IU, and verapamil 10 mg until the venous effluent was clear (Othman et al, 2010)..
\n\t\t\tProper peri-operative fluid management is one of the most important aspects governing hemodynamic function in the surgical patient. Adequate hydration is an integral part of the anesthetic management during renal transplant. Adequate plasma volume is essential in maintaining cardiac output and hence tissue perfusion. The stable hemodynamic status of the recipient during kidney transplant surgery is usually associated with an initial good graft function. To decrease the incidence of postoperative acute tubular necrosis (ATN), a liberal hydration policy is usually employed intra-operatively. The systolic blood pressure is maintained between 130 and 160 mm Hg, and the CVP is maintained between 12 and 14 mm Hg (Ferris et al, 2003). Maintaining adequate CVP is especially important in pediatric recipients because reperfusion of an adult kidney graft after completion of anastomosis may divert a significant amount of cardiac output. Measuring the central venous pressure (CVP) is really an absolute requirement to ensure good plasma volume expansion. The pulmonary artery pressure also can be used to guide fluid therapy in patients with preoperative left ventricular dysfunction (Carlier et al,1982). Additionally, mean arterial pressure (MAP) less than 100 mmHg and plasma volume below 45 mL/kg at reperfusion of the graft are the usual risk factors for graft failure (Toth et al,1998). Blood flow to the allograft after reperfusion may predict its immediate function. The early graft function requires adequate perfusion that can be achieved by expansion of the intravascular volume of the recipients.
\n\t\t\t\tRecently, a study was designed to examine the time of maximum volume expansion relative to renal ischemia period in living-related recipients and its effect on graft perfusion and early renal function (Othman et al, 2010). The kidney recipients were randomly assigned in this study into to one of two hydration regimens. The hydration regimens that used were either the constant infusion rate (CIR) regimen or the CVP target (CVPT) regimen. The CIR group received normal saline at a constant infusion rate of a range 10 to 12 ml.kg-1.-1h from the start of surgery until the renal vessels were unclamped at the end of anastomosis. Isotonic saline 0.9% was infused using a volumetric infusion pump. The CVPT group received normal saline at two different CVPT phases. The first “pre-ischemia” phase was from the start of surgery until the renal artery in the donor kidney was clamped. During this time, saline was infused slowly to maintain the CVP at target within 5 mmHg. In the second “ischemia” phase, from clamping the donor renal artery until unclamping of the recipient renal artery after vascular anastomosis completion, normal saline was infused to maintain a CVPT of around 15 mm Hg. Systolic, diastolic, mean arterial blood pressure, and CVP values were recorded 30 minutes after induction of anesthesia, at the time of renal artery clamping in the donor (onset of ischemia), at unclamping of the vessels after completion of the vascular anastomosis (end of ischemia), and at the end of surgery. Also renal ischemia time, concurrent saline infusion rate, time of onset of urine production on unclamping of the renal artery, and total urine output from unclamping of the renal vessels to the end of the surgery were recorded. Kidney turgidity was evaluated blindly by the surgical team members on a 3-point scale: score I (soft graft), score II (moderately turgid graft), and score III (highly turgid and firm graft).After surgery, all patients were assessed for the presence of tissue edema, especially in the conjunctiva, eyelids, face, and upper airway. Postoperative graft function was evaluated by estimation of fraction extraction sodium ratio (FENa %) after surgery to assess renal concentrating power: Daily serum creatinine, creatinine clearance, and total urine output were recorded for five days postoperatively. Patients in the CVPT group showed better intraoperative graft turgidity, arterial blood pressure stability, earlier diuresis, and rapid improvement of postoperative graft function. This was achieved in the CVPT group without an overall increase in infused saline volume (ranged 3 liters), vasopressor use, and diuretic doses compared with the CIR. The biphasic hydration regimen applied in the CVPT group with delayed most of the crystalloid administration until shortly before the renal vessels were unclamped (with a calculated range of 45-50 ml/min during ischemia time) had more favorable outcome.
\n\t\t\t\tHypotension may occur after unclamping the renal vessels and reperfusion of the graft. It is important to maintain the blood pressure because renal function is critically dependent on adequate perfusion. The two main factors that may precipitate to immediate revascularization hypotension:
\n\t\t\t\tSudden shift of 25% of cardiac output to the renal graft.
Release of vasodilator mediators accumulated during renal ischemia period.
It is critical that the patient is adequately hydrated throughout renal transplant surgery in preparation for reperfusion of the graft. Close monitoring of the CVP, and avoidance of deep level of anesthesia during this period can prevent hypotension. The use of vasopressors with α agonist action may comprise blood flow to the transplanted organ. Additional fluid may be required to maintain blood pressure and replace urine output. Furosemide can enhance urine output. Loop diuretics block the Na+/K+ channels in the thin ascending loop of Henle. This prevents reabsorption of electrolytes in this part of the nephron. The high osmolar fluid then prevents reabsorption of water in the distal tubule. A large volume of fluid with high electrolyte content is excreted. Mannitol is freely filtered in the glomerulus, but not reabsorbed. It causes osmotic expansion of urine volume. Loop diuretics and /or mannitol may be used to promote diuresis from the grafted kidney. Mannitol improves renal blood flow, acts as a free radical scavenger and reduces the incidence of impaired renal function immediately after transplant (Kasper et al, 2005).
\n\t\t\t\tAnother study was previously done for pediatric kidney recepients used average introperative fluids 88 ml/kg with a wide range of 30-90 ml/kg which reflected a large range of preoperative hydration status of recipients. However, younger children received higher volume of fluids per kilogram than older one. Also this study indicated that there was no correlation between the amount of fluid given intraoperatively and the occurrence of postoperative oliguria or acute tubular necrosis. (Coupe et al 2005).However, the intraoperative fluid replacement during kidney transplantation should be carefully titrated to the needs and overload must be avoided to get ride the problems that may developed if the new graft is either delayed to function or failing.
\n\t\t\tThe choice of a particular solution in a given clinical situation may be guided by an understanding of the solutions’ properties, but there is still an ongoing debate on the relative merits of crystalloid and colloid solutions for kidney recipients.The intravenous administration of adequate volumes of fluid is associated with earlier onset of graft function, lower postoperative serum creatinine, higher postoperative creatinine clearance, reduced incidence of delayed graft function, and improved graft survival. Most anesthesiologists avoid potassium-containing fluids during renal transplantation with the belief that it may worsen hyperkalemia in case of impaired graft function. The administration of normal saline and normal saline-based fluids (5% albumin) is the standard of care for fluid management in patients undergoing renal transplant surgery. This policy is primarily based on avoidance of potassium-containing fluids that can contribute to intra-operative hyperkalemia. The recipient\'s blood is usually typed and screened preoperatively. However, blood loss is usually minimal during uncomplicated kidney transplantation. Also blood transfusion is unlikely practice for kidney recipients except in highly indicated cases because of high possibility of triggering the patient\'s immune system. The anesthesiologist should attempt to maintain a mean blood pressure range of 60 to 80 mm Hg, central venous pressure (CVP) between 10 to 14 cm H20 and mean pulmonary artery pressure of 18 to 20 mm Hg. The estimated blood loss during the case is usually minimal (< 300 ml). In some cases, greater blood loss may require transfusion of packed red cells. Packed red cells should be cytomegalovirus (CMV) negative.
\n\t\t\tCrystalloids solutions are usually preferred during kidney transplantation to correct fluid and electrolyte imbalance (Table 1). However in certain situation as in severe hypovolemia, colloids may be valuable. A great source of controversy and debate is the choice of intra-operative fluid during kidney transplantation. In a survey conducted in over 90% of renal transplant centers in USA, normal saline was used for hydration during kidney transplantation (O\'Malley et al 2002). Many studies have shown that the use of normal saline leads to a major increase in serum potassium compared with Ringer’s lactate, most likely due to associated hyperchloremic metabolic acidosis through an extra cellular shift of potassium (O\'Malley et al, 2005; Khajavi et al, 2008).
\n\t\t\t\tAdditives (bicarbonate) | \n\t\t\t\t\t\t\tMg++ mMole/l | \n\t\t\t\t\t\t\tCa++ mMole/l | \n\t\t\t\t\t\t\tK+ mMole/l | \n\t\t\t\t\t\t\tCl- mMole/l | \n\t\t\t\t\t\t\t+Na mMole/l | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
- | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t154 | \n\t\t\t\t\t\t\t154 | \n\t\t\t\t\t\t\tNormal Saline (0.9%) | \n\t\t\t\t\t\t
Lactate(28) | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t1.5 | \n\t\t\t\t\t\t\t4 | \n\t\t\t\t\t\t\t109 | \n\t\t\t\t\t\t\t130 | \n\t\t\t\t\t\t\tLactated Ringer\'s | \n\t\t\t\t\t\t
Acetate(28) | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t1.5 | \n\t\t\t\t\t\t\t4 | \n\t\t\t\t\t\t\t109 | \n\t\t\t\t\t\t\t130 | \n\t\t\t\t\t\t\tAcetated Ringer\'s | \n\t\t\t\t\t\t
Acetate (27) + Gluconate(23) | \n\t\t\t\t\t\t\t3 | \n\t\t\t\t\t\t\t1.5 | \n\t\t\t\t\t\t\t5 | \n\t\t\t\t\t\t\t98 | \n\t\t\t\t\t\t\t140 | \n\t\t\t\t\t\t\tPlasmalyte | \n\t\t\t\t\t\t
Commonly used crystalloids and their composition:
Hyperchloremia may have adverse renal effects through vasoconstriction in afferent and efferent arteriolar beds of kidney and may result in a decrease in the urine output (Wilcox, 1983). Consequently, the use of Ringer’s lactate is now preferred in renal transplant surgery. It is essential to acknowledge that intravenous fluids are behaved like drugs with indications, contraindications, and side effects. With this in mind, the anesthetist must carefully choose the type of fluid for intra-operative use during kidney transplantation.This choice is based on number of factors. These factors include the physical properties of the solution, the patient\'s biochemical profile with special reference of serum electrolytes and surgical circumstances.
\n\t\t\t\tThe principal component of crystalloid fluids is the inorganic salt sodium chloride (NaCl). Sodium is the most abundant solute in the extracellular fluids, and it is distributed uniformly throughout the extracellular space. Because 75 to 80% of the extracellular fluids are located in the extravascular (interstitial) space, a similar proportion of the total body sodium is in the interstitial fluids. Exogenously administered sodium follows the same distribution, so 75 to 80% of the volume of sodium-based intravenous fluids are distributed in the interstitial space.This means that the predominant effect of volume resuscitation with crystalloid fluids is to expand the interstitial volume rather than the plasma volume. An infusion of 1 L of 0.9% sodium chloride (isotonic saline) adds 275 mL to the plasma volume and 825 mL to the interstitial volume. Note that the total volume expansion (1100 mL) is slightly greater than the infused volume. This is the result of a fluid shift from the intracellular to extracellular space, which occurs because isotonic saline is actually hypertonic to the extracellular fluids.
\n\t\t\t\tThe prototype crystalloid fluid is 0.9% sodium chloride (NaCl), also called isotonic saline (osmolarity=308 mOsmole/l) or normal saline. The latter term is inappropriate because a one normal (1 N) NaCl solution contains 58 g NaCl per liter (the combined molecular weights of sodium and chloride), whereas isotonic (0.9%) NaCl contains only 9 g NaCl per liter. The pH of isotonic saline (pH=5.7)is also considerably lower than the plasma pH. These differences are rarely of any clinical significance. The chloride content of isotonic saline is particularly high relative to that of plasma (154 mEq/L versus 103 mEq/L, respectively), so hyperchloremic metabolic acidosis is a potential risk with large-volume isotonic saline infusion.
\n\t\t\t\tRinger’s solution was introduced in 1880 by Sydney Ringer, a British physician and research investigator who studied mechanisms of cardiac contraction. The solution was designed to promote the contraction of isolated frog hearts, and contained calcium and potassium in a sodium chloride diluent. In the 1930s, an American pediatrician named Alexis Hartmann proposed the addition of sodium lactate buffer to Ringer’s solution for the treatment of metabolic acidoses. The lactated Ringer’s solution, also known as Hartmann’s solution, gradually gained in popularity and eventually replaced the standard Ringer’s solution for routine intravenous therapy.
\n\t\t\t\t\tLactated Ringer’s solution contains potassium and calcium in concentrations that approximate the free (ionic) concentrations in plasma. The addition of these cations requires a reduction in sodium concentration for electrical neutrality, so lactated Ringer’s solution has less sodium than isotonic saline. The addition of lactate (28 mEq/L) similarly requires a reduction in chloride concentration and has pH approximate 6.7. The chloride in lactated Ringer’s is more closely approximates plasma chloride levels than does isotonic saline. Lactated Ringer\'s is also not an ideal crystalloid.The calcium in lactated Ringer’s can bind to certain drugs and reduce their bioavailability and efficacy.Also,lactated Ringer\'s is considered a moderately hypotonic (Osmolarity=273 mOsmaole/l) crystalloid solution. So, many studies recommend limited use of lactated Ringer\'s in patients who at risk of cerebral edema (Feldman et al; 1995).
\n\t\t\t\tAcetated Ringer\'s isolution is similar in its compostion to lactated ringer\'s except replacement the lactate with acetate which could converted to bicarbonate in all body cells including muscles(Hahn &Drobin, 2003).
\n\t\t\t\tPlasmalyte is a balanced salt solution having electrolyte compostion and osmolarity (294 mOsmole/l) similar to that of plasma.The major feature of these solutions is the added buffer capacity, which gives them a pH that is equivalent to that of plasma (pH=7.4). Acetate and gluconate content act as precursors of bicarbonate. This converstion occur predominantly in the liver,although acetate could be converted to bicarbonate in other body tissues resulting in less acidosis.An additional feature is the addition of magnesium, which may provide some benefit in light of the high incidence of magnesium depletion in hospitalized patients.A previous relevant study, which compared different crystalloid solutions on acid-base balance and early kidney functions after kidney transplantation,have concluded that plasmalyte has the best metabolic profile ( Hadimioglu et al, 2008).
\n\t\t\t\tNatural available colloid as human albumin has been widely applied for the treatment of hypovolemia in critically ill and surgical patients during the last two decades. Albumin is being widely replaced by many synthetic colloids such as dextrans, gelatins, and hetastarch (HES) solutions. Colloids are stayed in the intravascular compartment because of their macromolecules composition. The degree of plasma volume expansion exerted by colloids is determined by their concentration, molecular weight, chemical structure, colloid osmotic pressure, metabolism, and elimination rate. HES solutions have varying effects on coagulation characteristics, which depend on the size of the HES molecules and the degree of hydroxethyl substitution. Impaired platelet function, and impaired coagulation profile as measured by thromboelastography have been reported to arise during the administration of HES. This raises some concern for end stage renal patients undergoing kidney transplantation, because they are prone to bleeding complications because of associated platelet dysfunction (Boccardo et al; 2004). Although it is rare, severe and life-threatening anaphylactic reactions have been reported in association with any of the commonly used semi-synthetic colloids and with albumin. The incidence of severe anaphylactic reactions is probably more frequent for gelatins (0.35%) and for dextrans (0.27%) than for albumin (0.10%) or for starches (0.06%) This required to be considered when weighing the risks/benefits for the use of different plasma volume expanders (Laxenaire et al ;1994). A study with a large series of renal transplants from deceased donors, revealed a statistically significant benefit from the usage of albumin, though mannitol, furosemide, and electrolyte solutions were administered concomitantly ( Dawidson et al;1992). Protective properties to the intra-operative administration of mannitol during the vascular phase were attributed to the osmotic diuretic and the antioxidant properties of sugar alcohols substances. Two of the synthetic colloids that have widely replaced albumin in clinical practice – dextrans and gelatins – do not seem on the whole to be preferable to albumin. An old comparative study comparing intra-operative albumin and dextran-40 in renal transplant recipients from a living related donor did not show any significant difference between the two regimens with regards to urine volume output and serial serum creatinine concentrations after transplantation (Dawidson et al; 1987). The clinical value of this study may be limited, because small sample size (17 patients) had no enough statistical power to detect outcome differences. Dextran solutions have been associated with major side-effects, such as coagulation disorders, severe anaphylactic reaction, and acute tubular necrosis.This has led to major limitation for their usage as plasma volume expansion in kidney transplantation (Bergman et al; 1990).
\n\t\t\t\tHetastarch (HES) solutions (table 2) are originally synthesized from natural polymers of amylopectin. The pharmacokinetics of HES solutions depend on their molecular weight and C2/C6 hydroxyethylation ratio which influences their degradation mainly by plasma amylase. Osmotic, nephrosis-like lesions were reported in 80% of transplanted kidneys after the use of routine volumes of HES 200/0.6 in brain-dead donors (Legendre et al,1993). The likely mechanism for this action may be swelling and vacuolization of the tubular cells, and tubular obstruction due to hyper-viscous urine. Additionally, the slow degradation of high molecular weight or highly substituted HES may increase plasma osmotic pressure, leading to renal dysfunction and therefore these factors limit their use during kidney transplantation. The latest HES generation, HES 130/0.4, has a total body clearance about 23–31 times faster than that of the first generation hetastarch, and exhibits the best risk/benefit ratio of all available HES (Jungheinrich, and Neff,2005).
\n\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t | HES 70/0.5 | \n\t\t\t\t\t\t\tHES 130/0.4 | \n\t\t\t\t\t\t\tHES 200/0.5 | \n\t\t\t\t\t\t\tHES 200/0.5 | \n\t\t\t\t\t\t\tHES 200/0.62 | \n\t\t\t\t\t\t\tHES 450/0.7 | \n\t\t\t\t\t\t
Concentration (%) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | 6 | \n\t\t\t\t\t\t\t6 | \n\t\t\t\t\t\t\t6 | \n\t\t\t\t\t\t\t10 | \n\t\t\t\t\t\t\t6 | \n\t\t\t\t\t\t\t6 | \n\t\t\t\t\t\t
Volume efficacy (%) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | 100 | \n\t\t\t\t\t\t\t100 | \n\t\t\t\t\t\t\t100 | \n\t\t\t\t\t\t\t130 | \n\t\t\t\t\t\t\t100 | \n\t\t\t\t\t\t\t100 | \n\t\t\t\t\t\t
Volume effect (hours) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | 1-2 | \n\t\t\t\t\t\t\t2-3 | \n\t\t\t\t\t\t\t3-4 | \n\t\t\t\t\t\t\t3-4 | \n\t\t\t\t\t\t\t5-6 | \n\t\t\t\t\t\t\t5-6 | \n\t\t\t\t\t\t
Mean molecular weight (KD) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | 70 | \n\t\t\t\t\t\t\t130 | \n\t\t\t\t\t\t\t200 | \n\t\t\t\t\t\t\t200 | \n\t\t\t\t\t\t\t200 | \n\t\t\t\t\t\t\t450 | \n\t\t\t\t\t\t
Molar substitution | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | 0.5 | \n\t\t\t\t\t\t\t0.4 | \n\t\t\t\t\t\t\t0.5 | \n\t\t\t\t\t\t\t0.5 | \n\t\t\t\t\t\t\t0.62 | \n\t\t\t\t\t\t\t0.7 | \n\t\t\t\t\t\t
C2/C6 ratio | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | 4:1 | \n\t\t\t\t\t\t\t9:1 | \n\t\t\t\t\t\t\t6:1 | \n\t\t\t\t\t\t\t6:1 | \n\t\t\t\t\t\t\t9:1 | \n\t\t\t\t\t\t\t4.6:1 | \n\t\t\t\t\t\t
Characteristics of different available hydroxyethyl starch (HES) solutions.
HES preparations (table 2) are characterized by the following criteria:
\n\t\t\t\t(A) Concentration (6%, 10%),
\n\t\t\t\t(B) Molecular weight (Mw: the sum of each molecule‘s weight devided by the total
\n\t\t\t\tmixture’s weight times the weight of the molecule):
\n\t\t\t\tLow-molecular weight [LMW]-HES: 70,000 dalton.
Medium-molecular weight [MMW]-HES: 130,000 to 260,000 dalton.
High-molecular weight [HMW]-HES: > 450,000 dalton,
(C) Molar substitution (MS: the molar ratio of the total number of hydroxyethyl groups to the total number of glucose units):
\n\t\t\t\tLow MS: 0.4 and 0.5
Moderate MS: 0.62
High MS: 0.7
(D) C2/C6 ratio. The ratio of the C2:C6 hydroxyethylation appears to be key factors for pharmcokinetic behaviour of HES and possibly also for its side effects (e.g. accumulation).
\n\t\t\t\tHowever, there still some debates surrounding the effects of hetastarch solutions on renal function, especially in the field of kidney transplantation.
\n\t\t\t\tOver the last few decades, there has been a shift in anesthesia practice from using natural colloids such as blood, albumin and fresh frozen plasma to synthetic colloids.However, the widespread use of synthetic colloids during kidney transplantation is still need more investigations to confirm their safety.
\n\t\t\t\tThe evidence for Targeted Fluid Administration suggests that administration of colloid provides benefits over crystalloids. However no head-to-head trials of crystalloid versus colloid or colloid versus colloid during kidney transplantation have been performed.
\n\t\t\t\tLikewise all the clinical trials of Targeted Fluid Administration used are saline-based fluids. A new controversy surrounds the adequate amount of peri-operative fluid administration. For decades the strategy has been to keep the patient normovolaemic (‘well hydrated’) in the perioperative period. Early urine production is important in kidney transplantation as a good prognostic factor. It is usually associated with longer graft survival and lower morbidity. Early diuresis is commonly observed in live donor grafts. In dead donor grafts, onset of diuresis is usually delayed due to the variable period of kidney ischemia and their storage at low temperatures in electrolyte solutions until they are implanted. Some measures, such as the administration of large volumes of liquids and diuretics, have been advocated to obtain good diuresis at the end of the surgery. Mannitol induces osmotic diuresis and also has a protective effect on the tubular cells of transplanted kidney from ishaemic injury. The renal protective agents as mannitol used during kidney transplantation seems to be related to its ability to increase renal blood flow. This presumably is due to the result of release of intrarenal vasodilator prostaglandin and atrial naturetic peptide. Also, loop diuretics as furosemide act by blocking the Na+/K+ ATPase channels present in the thin ascending limb of Henle, decreasing tubular oxygen consumption which may offer some protection against ischemic injury( Esson and Schrier;2002).
\n\t\t\t\tHypotension may occur after unclamping the vessels and reperfusion of the graft. It is important that the patient should be well hydrated, as renal function is critically dependent on renal perfusion. It is especially important in paediatric recipients because reperfusion of an adult size graft may divert a significant amount of their own blood volume. A previous study for special fluid strategy in pediatric kidney transplantation, a total mean volume of 18 ml.kg-1.h-1was infused, which divided to include approximately 8 ml.kg-1.h-1 of crystalloid, 7 ml.kg-1.h-1 of fresh frozen plasma, and 2 ml.kg-1.h-1 of washed red blood cells( Yamamoto et al 2003).
\n\t\t\t\tCentral venous pressure value may decrease around 50% within two hours after revascularization despite aggressive fluid management. This decline is similar in recipients of both cadaveric and living related kidney donor and the cause may be multi-factorial such as redistribution of fluids, changes in vascular permeability or increased nitric oxide levels. The use of vaso-pressors,with alpha agonist activity, are better to be avoided as they can compromise blood flow to the transplanted kidney. Loop diuretics, and mannitol may be used to enhance urine production. Low dose dopamine was previously used to stimulate dopaminergic receptors (DA1) in the kidney vasculature to induce vasodilatation and increased urine output. However, the utility of this approach is questioned in a denervated kidney, which it may not respond adequately to a low dose of dopamine as normal kidneys do.
\n\t\t\tStandard ASA monitors are adequate, although, patients with more advanced co-morbid conditions require more extensive monitoring such as continuous arterial blood pressure and pulmonary artery monitoring. Routine monitors include noninvasive arterial blood pressure, ECG, core temperature, end-tidal carbon dioxide (ETco2), and arterial oxygen saturation SpO2. CVP monitoring is required for all patients in order to guide volume management and for postoperative vascular access..Arterial monitoring is reserved for small children undergoing anastamosis of the allograft to the great vessels. Older children undergoing anastamosis to the iliac vessels do not require arterial monitoring, and in fact it should be avoided in order to preserve sites for future arteriovenous fistulae. Swan-Ganz monitoring of pulmonary artery pressures may be necessary in the infrequent patients with symptomatic hypertensive cardiomyopathy or with symptomatic cardiac dysfunction. All patients have urinary catheters inserted prior to surgery for urine output records. Laboratory investigations every 1-2 hours to follow blood hemoglobin,Hct, serum K+ and acid-base status. Those with the severe co-morbid conditions, such as symptomatic coronary artery diseases or history of congestive heart failure, should be monitored with a non-invasive transesophageal echocardiography to monitor cardiac functions.
\n\t\tStrict monitoring of fluid input and urine output is essential especially in the early postoperative period to guide the function of the new graft. A study showed that recipients of living donor kidneys lost more serum albumin during surgery than their donors, resulting in decreased plasma volume that was associated with reduced post-operative urine output. Therefore, it was recommended that administration of postoperative colloids administration is necessary to replace the additional loss of albumin during transplant surgery (Dawidson et al; 1987). On the first day after successful transplantation, serum creatinine concentration is usually related to mean arterial blood pressure. It is decreased in patients with mean arterial pressure (MAP) above 100 mmHg, whereas it remained stable in patients with MAP of 80–100 mmHg and increased in patients with MAP below 80 mmHg (Toth et al ;1998). Post operative daily graft function was evaluated in another recent study that compared the CVP target regimen(15 mmHg) with constant infusion regimen(10-12 ml.kg-1.hour-1) during transplantation (Othman et al; 2010).It was based on the renal concentrating ability, as reflected by the fractional excretion of sodium (FENa% ) for 6 hours in immediate postoperative time. Also, serum creatinine level, creatinine clearance, and urine output were monitored daily for 5 days after surgery. This study reflected early postoperative faster decrease of serum creatinine with higher creatinine clearance and larger urine output in the CVP target group.This finding could attest to the sustained benefit of the central venous pressure titration approach over the constant infusion approach..FENa % may be affected by a high diuretic dose that acts by altering the handling of sodium by the kidney. In this study, all patients in the constant infusion regimen group and only 50% of patients in the CVPT group had received variable large doses of furosemide, which might account for the early decrease of FENa %. Therefore, FENa % may be not useful as a renal function test for comparison between the used hydration regimens (Othman et al ; 2010).
\n\t\t\tMaintenance of crystalloid hydration during postoperative period must be adjusted accordingly to vital signs and urine output. Replace urine output (ml per ml) with crystalloid selected according to graft function and patient serum electrolytes. A rigorous postoperative intravenous hydration protocol in renal transplant recipients may protect against vascular thrombosis. Delayed graft function is mainly defined as the need for dialysis in the first week after transplant. It may result from a collection of various detrimental factors such as recipient\'s age, tissue match and any surgical complications as vessel thrombosis or bleeding. One-year graft survival of a first transplant is approximately 95%; for recipients of non-identical living-related kidneys, it approximates to 90%; for recipients of cadaver kidneys, it approximates 80%; and for re-transplanted recipients of cadaver kidneys, it is usually less to approximate 70%. Overall, recipient survival of approximately 95% during the first post-transplant year can be expected, although cardiovascular deaths remains a major concern (Flechner ; 1994).
\n\t\t\tPostoperative fluid management plan for kidney transplantation should be judicious and be modified in favor of maintaining just adequate filling pressures to maintain adequate intravascular volume and baseline hemodynamics.Additional fluids as per need once urine output from the new graft starts to decline guided by CVP and myocardial function and avoid overload that may empress the heart function with the recommendation of dialysis in presence of delayed graft function or acute tubular necrosis.
\n\t\tGraft viability associated with renal transplantation is a product of the proper managing of the kidney donor, the allograft, and the recipient patient. Short- and long-term outcome is influenced by perioperative fluid policy. The function of the transplanted kidney seems to be optimized if graft perfusion is greatly maximized through good hydration policy with CVP target to approximate15 mmHg. A strategy of crystalloid administration to a target central venous pressure resulted in better stability of intraoperative blood pressure, less use of vasopressors and furosemide. This could induce a faster decrease in serum creatinine towards normal vlue. Perioperative close monitoring of recipients and optimization of intravascular fluid volume status to maximize graft perfusion are the usual keys for long-term success of renal transplants. Crystalloids are usually considered as the first choice and some colloids could be used safely as alternatives during the procedure and in early postoperative periods. The ideal crystalloid solution seems resemble the plasma composition with special reference to electrolyte content.Although, lactated and acetated Ringer\'s solutions are moderately hypo-osmolar, isotonic normal saline has high chloride content that could induce hyperchloermic acidosis. Both lactate and acetate are considered as precursors of bicarbonate where lactate converted to bicarbonate in the liver and acetate converted to bicarbonate in all body tissues resulting in less acidosis. A mixture of normal saline with either lactated or acetated Ringer\'s solution may be the preferred crystalloid choice of fluid therapy during kidney transplantation. This policy could provide better guidance for perioperative hydration strategy during kidney transplantation until best evidence and multi-center guidelines will be established based upon more research in this field.
\n\t\tChronic obstructive pulmonary disease (COPD) is among the five leading causes of death in developed world [1]. Prevalence of COPD is constantly increasing. COPD has a high impact on patients’ wellbeing, healthcare utilization, and mortality [2] and causes a substantial and increasing economic and social burden [3, 4]. Cigarette smoking is clearly the predominant cause but other environmental agents including biomass fuel and air pollution may play a role as well. Common symptoms of COPD patients are chronic and progressive dyspnea, cough, and sputum production. These symptoms can be disabling and lead to activity limitation and ultimately inability to work and take care of themselves [5]. This vicious circle of inactivity that begins with breathlessness is because of peripheral muscle dysfunction [6], and dynamic hyperinflation [7].
\nFor several decades, treatment of COPD has been focused on smoking cessation, and pharmacological but with ever-increasing literature, intense exercise programs like pulmonary rehabilitation (PR) have become an integral part of management of COPD [8]. PR has been shown to be the most effective non-pharmacological intervention for improving health status in COPD patients and has become a standard of care for these patients [2]. PR and pharmacological therapy are not competitive but rather, must work closely together, if they are to result in a more successful outcome [9].
\nDespite increasing awareness on positive impact of rehabilitation in COPD, it remains underutilized in most countries. Lack of understanding on the benefits of a PR program, in addition to the incremental cost to the management, has hindered the widespread adoption of comprehensive PR for COPD patients [9]. This chapter aims at highlighting the impact of PR on patients with COPD, focusing on the clinical usefulness of PR. We also hope to stimulate primary care and pulmonary physicians to use PR more often.
\nPhysical therapy has been incorporated into the treatment of pulmonary patients as far back as the First World War. Winifred Linton, a British nurse, first felt the need for physical therapy while treating traumatic respiratory complications during the war. Following the war, she entered physical therapy training and began to teach localized breathing exercises to other physical therapists (PTs) and surgeons at the Royal Brompton Hospital in London. A few physical therapists in the United States were instructed in airway clearance techniques and began to use and teach them to patients during the polio epidemic of the 1940s [10, 11]. Rehabilitation programs for patients with COPD have existed for more than three decades and were incorporated into ATS official statement in 1981 [12]. Comprehensive and multidisciplinary approach to the pulmonary rehabilitation programs have remained the key to its success over several years. It involves a team effort from physical therapist, respiratory therapist, nurses, physician and other support staff.
\nPulmonary rehabilitation has been defined as a comprehensive program which is individual patient focused and includes exercise training, education, and behavior change. It has been found to help improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors [13].
\nPulmonary rehabilitation has demonstrated physiological, symptom reducing, psychosocial, and health economic benefits in multiple outcome areas for patients with chronic respiratory diseases [14]. PR is appropriate for most patients with COPD. Improved functional exercise capacity and health-related quality of life has been demonstrated across all grades of COPD severity, although the evidence is strong in patients with moderate to severe disease [15].
\nBeside respiratory symptoms of dyspnea, COPD has been established to have extra-pulmonary manifestations. Some on them involve skeletal muscle dysfunction which results from physical inactivity and systemic inflammation in addition to hypoxemia, undernutrition, oxidative stress and systemic corticosteroid [16, 17].
\nPeripheral muscle dysfunction seen in COPD patients is a result of multitude of pathophysiological changes occurring in the skeletal muscles. Skeletal muscles in COPD patient have decreased oxidative capacity that can lead to early lactic academia [18, 19, 20], decreased muscle fiber volume [21], redistribution of the muscle fiber type (from type 1 to type 2 fibers) [21, 22, 23], and abnormal muscle fiber capillarization [23]. These changes in the structure and functioning of the skeletal muscles can lead to higher concentration of lactate for a given work. This in turn can lead to increased ventilation, resulting in dynamic hyperinflation and overall increased ventilator burden. With muscle dysfunction there is a limitation in the activity and promotion of a sedentary lifestyle. A sedentary lifestyle inevitably leads to social isolation, depression and physical deconditioning. Exacerbations of COPD also promote the reduction of exercise performance, dyspnea, and the loss of Health-related quality of life (HRQoL) [24].
\nPR has no direct impact on lung mechanics or gas exchange [25]. Rather, it optimizes the function of other body systems so that the effect of lung dysfunction is minimized [26]. A comprehensive PR program can help COPD patients gradually improving muscle function by changing muscle biochemical structure. This leads to improved tolerance for higher work load in the patients [27]. PR additionally reduces the central perception of dyspnea and dynamic hyperinflation [28].
\nA usual pulmonary rehabilitation program can range anywhere from 6 weeks to 12 weeks at various centers which incorporate aerobic exercise, education, muscle strengthening etc. Usually patients undergo supervised training 2–3 times a week, for 30–60 minutes in each session. This could include any regimen for endurance training, interval training, resistance/strength training, walking exercises, flexibility, inspiratory muscle training and/or neuromuscular electrical stimulation. The interventions are individualized to maximize personal functional gains.
\nThere are several benefits of PR not limited to improvement in symptoms like dyspnea, exercise tolerance and overall health status in stable patients.
\nPR results in reduction in symptoms of dyspnea and leg discomfort. Patients notice improved limb muscle strength and endurance. Most patients also experience improved functional capacity with more independence in activities of daily living (ADLs) [29]. In a Cochrane review [30] including 23 randomized controlled trials, PR was found to relieve dyspnea, and fatigue, improved emotional function and patient’s sense of control over their condition. All these improvements were large and statistically significant.
\nThere has been increasing interest in physical activity, as inactivity has been linked with reduced survival, poorer quality of life and increased healthcare utilization [31]. In the same Cochrane review as above [30], patients were noted to have improved exercise capacity. Other studies from Griffith’s et al. and Singh et al. have suggested similar findings [32, 33].
\nPR has also been found to reduce unscheduled healthcare visits, COPD exacerbation and hospitalization in some literature [34]. Rubi et al. reported reduction in COPD exacerbation, hospitalization and days of hospitalization in 82 consecutive patients [35]. In fact, there is some literature to suggest reduced hospitalization in patients participating in PR programs immediately after acute exacerbation of COPD (AECOPD) beginning within 1 week of discharge [36].
\nAnxiety and depression affect significantly in COPD patients leading to worse patient centered outcomes. Tselebis et al. conducted study in 101 consecutive patients and noted that psychological morbidity was improved with participation in PR program irrespective of severity of the disease (COPD) [37]. This was confirmed in a meta-analysis of six RCTs which indicated that pulmonary rehabilitation was more effective than standard care for the reduction of anxiety and depression [38].
\nHRQoL was noted to be significantly improved in patients with COPD participating in PR as well [34, 39]. The St. Georges Respiratory Questionnaire Scores were used in a meta-analysis, which showed significant improvement in HRQoL following pulmonary rehabilitation [40]. An early RCT compared pulmonary rehabilitation with education alone and demonstrated that self-efficacy improved in the intervention group [41].
\nCOPD patients have been known to have improved mortality with cessation of smoking. There is some signal that an association exists between completion of PR and survival based on a retrospective analysis involving 1515 patients [42]. But a systematic review conducted of two randomized control trials showed significant survival benefit at 1 year in one trial but no significant benefit with another study at end of 3 years. Neither of the study was powered to really derive the desired outcome [43].
\nPatients with chronic lung condition who have symptomatic shortness of breath limiting their physical activity despite optimal medical management should be considered for pulmonary rehabilitation [44]. Patients with chronic diseases other than lung such as heart failure, musculoskeletal disease have the same benefit form pulmonary rehabilitation as patients with disabling lung conditions like chronic obstructive pulmonary disease, restrictive lung disease, and pulmonary hypertension. Pulmonary rehabilitation can markedly change the course of the disease if provided at an earlier stage of disease. This is due to improved exercise tolerance and physical activity, reduced exacerbations and improved self-efficacy and behavior change after pulmonary rehabilitation. [45]
\nOne of the most important indicator for referral to pulmonary rehabilitation is based on the modified Medical Research Council Breathlessness (mMRC) score (see Table 1) [46]. The mMRC scale is a 0–4 grade scale used to establish levels of perceived respiratory disability. It allows patients to indicate the extent to which their breathlessness affects their mobility [45, 46].
\nGrade | \nLevel of breathlessness with the activities | \n
---|---|
0 | \nNo shortness of breath except on strenuous exercise | \n
1 | \nShort of breath when walking on an incline | \n
2 | \nWalks slower than contemporaries on a level ground because of shortness of breath or has to stop due to breathlessness when walking up at own pace | \n
3 | \nStops for breath when walking 100 m or after a few minutes on level ground | \n
4 | \nToo short of breath to leave the house, or short of breath when dressing and undressing | \n
The modified Medical Research Council Breathlessness (mMRC) score.
It has been strongly recommended that patients with an mMRC dyspnea score of 2–4 who are functionally limited by breathlessness should be referred for pulmonary rehabilitation. However, benefits of pulmonary rehabilitation have also been seen in patients with an mMRC dyspnea score of 1 who are functionally limited by breathlessness. Patients with COPD who have an mMRC score of 4 achieve similar benefits from the pulmonary rehabilitation as those with a lower breathlessness score [47].
\nOther frequent indications for referral to a pulmonary rehabilitation program include poor functional status, physical deconditioning, chronic fatigue, poor health-related quality of life and difficulty performing activities of daily living. Patients who are requiring increased use of medical resources due to frequent exacerbations, hospitalizations and emergency room visits also benefit from pulmonary rehabilitation.
\nCandidates for lung volume reduction surgery for severe emphysema or for lung transplantation are also good candidates for PR [48]. Patients with COPD have shown improvements following a pulmonary rehabilitation program irrespective of their age or gender [49, 50, 51].
\nLevel of functional impairment [47, 52, 53] or disease severity does not affect the benefits seen in COPD patients with pulmonary rehabilitation program [54, 55]. A program of PR may be proposed in stable COPD as well as immediately after COPD exacerbation [56].
\nThere are very few exclusion criteria for a referral to pulmonary rehabilitation, which includes patients with the following conditions [45, 46]:
Unstable cardiovascular disease, uncontrolled diabetes and an ongoing orthopedic illness that will refrain patient from exercising.
Inability to do exercise safely because of any other medical illness like severe arthritis, severe peripheral vascular disease.
Untreated psychiatric illness and cognitive impairment which makes it hard for patients to follow directions are other reasons for not referring a patient to pulmonary rehabilitation.
Lack of motivation is another exclusion criterion for pulmonary rehabilitation.
Adherence to pulmonary rehabilitation program is critical to see the ongoing benefits from the program. However, non- adherence and high dropout rate of 20–30% is reported in the studies listing predictive factors of non-adherence to pulmonary rehabilitation. These factors include [52, 53, 57, 58]:
Even though current smokers obtain the same benefits from pulmonary rehabilitation, smokers generally have poor adherence to pulmonary rehab than ex-smokers. Active smoking status is not an absolute contraindication for pulmonary rehabilitation. Patients are encouraged to undergo smoking cessation prior to pulmonary rehabilitation.
Depression and social isolation.
Lower quadriceps strength.
COPD patients with higher mMRC score and frequent exacerbations.
Long commute to pulmonary rehabilitation and lack of transport.
Cost of pulmonary rehabilitation.
Every patient referred for pulmonary rehabilitation should be thoroughly evaluated prior to initiation of the program. Majority of the patients have a regular pulmonary physician managing the lung disease. As a part of the management, pulmonary physicians refer the patient for pulmonary rehabilitation to supplement the pharmacological treatment. These patients when present to the pulmonary rehabilitation have already undergone an evaluation of symptoms and physical examination. Regardless, it is a good practice to perform a thorough evaluation of patient’s medical problems, laboratory results, social habits and specific medications. This should be accompanied by a comprehensive physical examination with estimation of patient’s functional capacity. In most of the pulmonary rehabilitation program, this assessment is performed by the physical therapists. If a pulmonologist is an integral part of the program, the physician can do this work up.
\nPrior to initiation of the pulmonary rehabilitation program, a careful appraisal of patient’s pulmonary disease and current severity should be done. For COPD patients this will include the duration of their symptoms, current symptomatology, mMRC score [46], smoking history, pulmonary function testing, arterial blood gas analysis, inhaler therapy, oxygen supplementation and non-invasive ventilation prescription. It is imperative that a special attention should be paid to patient’s co morbidities. This is essential as several other medical problems may have impact on patient’s disease course and exercise capacity. These may include obesity, OSA, diabetes, cardiovascular co morbidities, hypertension, osteoarthritis, pulmonary hypertension, peripheral vascular disease and malignancy.
\nA detailed pre rehab assessment enables the physical therapist to devise an individualized treatment plan for the patients. This strategy is particularly helpful for patients with advanced disease, low exercise tolerance, special healthcare needs such as high oxygen requirements, pacemaker or defibrillators, walkers and cane. Information gathered at the beginning of the program will help set realistic individualized goals and alert the provider regarding the possibility of adverse effects.
\nPhysical examination at the beginning of the pulmonary rehabilitation program is centered on measurements of patient’s functional status and capacity to handle additional physical stress. Most relevant for COPD patients will be an examination of muscle wasting, joint mobility, postural deformities, and cardio-respiratory examination. Results of this examination allows physical therapist to gauge individual patient’s tolerance and potential areas of improvement.
\nAn important component of physical examination is nutritional assessment. This commonly includes measurement of weight, height and BMI. Both being underweight and overweight in a COPD patient can be detrimental. Excess weight can lead to extrinsic restriction on lung capacity as well as increased work of breathing. Weight loss and muscle wasting is a poor prognostic factor in COPD patients [59, 60, 61].
\nPertinent respiratory examination in patients with COPD is directed at ability of the patients to clear their respiratory secretions, use of accessory muscles of respiration, breathing pattern, adventitious sounds on auscultation such as wheezing and crepitation. A knowledge of patients’ respiratory status will help develop an educational plan regarding self-management, medication compliance and respiratory muscle training.
\nReduced functional capacity due to physical deconditioning is widespread in COPD patients. This is multifactorial with poor nutritional status, systemic inflammation, cardiovascular comorbidities, postural deformities and osteoporosis [62] Interviewing the patient to ascertain their capacity to perform ADLs, sustained exercise and risk of falls is essential. Several questionnaires have also been used to objectively measure individual patient’s baseline functionality. A few examples include: the Functional Independence Measure (FIM), the Assessment of Motor and Process Skills (AMPS), and a Functional Capacity Evaluation (FCE) [63].
\nApart from questionnaire, various exercise tests can be used to gauge individual patient’s functional capacity. These exercise tests can be done as field walking tests, on bicycle ergometer or on treadmill. In most hospital, simple walk testing can be cost effective and practical. Walk tests are considered more reflective of daily functionality of a COPD patient. Some of the commonly employed walk tests include the 6-minute walk test (6MWT) and the incremental shuttle walk testing. Standardized protocols have been established for performing the 6MWT. If done as per the set protocol, this walk test is highly reproducible and reliable test for both diagnostic and prognostic purposes. In this test, patient walk back and forth on a 30-m distance marked hallway at their own pace for 6 minutes. During the test, distance walked, vital signs, oxygen desaturation, development of dyspnea using a visual analog scale is measured [64]. The incremental shuttle walk test is performed on a 10 m marked course. It is a paced walk test to assess symptom limited maximal exercise capacity. Test is continued until patient develops symptoms of dyspnea or for 20 minutes, whichever occurs first. This is a valid and popular testing in various resource limited clinical settings [45].
\nIf in addition to the functional limitation specific problems are identified by the physical therapists, various other tests may need to be performed. These tests address the muscle weakness, gait disturbances, and include balance testing and sit-to-stand tests [65].
\nAfter an initial assessment, patient is enrolled into a pulmonary rehabilitation program. The basic aim of such a program in any COPD patient is to assist them in performing essential daily activities with independence. Independence comes from reduction in dyspnea and fatigue. COPD patient are inadvertently caught in a downward spiral where dyspnea is leading to inactivity, which in turn leads to physical deconditioning and decreased capacity to handle day-to-day stress. To save the patient from this downward spiral a pulmonary rehabilitation program focuses on improving the cardiorespiratory endurance, muscle strength, body flexibility and respiratory muscle training. With an individualized patient’s clinical analysis and examination, a specific therapy plan can be built for each patient. This plan is intended to establish patient specific goals and focus on areas of functional limitation, which need to improve to achieve those goals. As the COPD patients undergo pulmonary rehabilitation, improvement in their physical deconditioning and exercise capacity needs to be measured and documented. This is achieved by using a variety of parameters, such as quantity of exercise performed or improvement in perception of dyspnea, symptoms, heart rate during exertion. Any changes seen in these parameters will be suggestive of patient’s improved capacity to handle the physical stress. As discussed earlier in the chapter walk tests and questionnaires can provide an objective measure of functional improvement for COPD patients undergoing pulmonary rehabilitation.
\nPhysical exercise training in COPD patients can be delivered in two forms: Continuous high intensity aerobic endurance training or an interval training, which alternates high intensity aerobics with low intensity exercises [66]. Continuous high intensity regimen of endurance training can be administered with constant load or incremental load. It has been shown that high intensity aerobic training (70–80% of peak work rate), will result in maximal improvement in physical fitness by increasing oxygen consumption, delaying anaerobic threshold and decreasing heart rate for a given exercise rate [27, 62, 67, 68, 69].
\nIn patients with advanced COPD and persistent dyspnea a high intensity endurance training is difficult to sustain. These patients can be provided with interval endurance training. In this approach, high intensity aerobic training in short bouts (30–180 s) is alternated with low intensity exercises (leading to a subjective experience of exertion between 4 and 6 on the modified Borg scale) or rest [70, 71, 72, 73, 74].
\nEven though there may be less appreciable gains in aerobic parameters, this training approach has proven to be effective in improving exercise endurance in COPD patients [42, 75]. Interval endurance training leads to lesser degree of pulmonary hyperinflation allowing patients to exercise longer without excessive dyspnea. COPD patients may more easily adapt a lower intensity exercise regimen in their daily life. The choice of regimen is ultimately based on both therapist and patient preference.
\nEndurance training is delivered using various modalities including walking (treadmill or supported ground walking with walker or wheelchair), cycling, rowing, and swimming or modified aerobic dancing. It is recommended to provide this training 3–5 times per week at an intensity aimed at a Borg Dyspnea score of 4–6 (moderate level of exercise) [26, 44, 48, 67, 69, 76, 77, 78, 79]. Exercise sessions can last from 30 to 120 minutes, with at least 30 minutes of continuous aerobic activity, based on each patient’s capacity [26, 46, 79, 80]. General recommendation for the frequency of pulmonary rehabilitation is two supervised exercise sessions a week with third unsupervised session based on the available resources [44, 81, 82]. A minimum of 12 exercise sessions or 4 weeks of rehabilitation program is essential to achieve any improvement in physical fitness. Program length can be increased up to 72 weeks if patient is inclined and insurance coverage is favorable [48, 83, 84]. While shorter (6–8 weeks) pulmonary rehabilitation programs are more cost effective and widespread, longer duration programs have shown sustained beneficial effects. This is mostly due to fact that longer duration programs not only lead to physiological changes but also behavioral changes [85].
\nMore specific for COPD patients it is recommended to check oxyhemoglobin saturation both prior to the start of the exercise and at peak work rate. This will not only help to ascertain the need for oxygen supplementation but also guide both therapist and the patient to know appropriate level to use with different intensity of work. Similarly, a careful attention on patient’s bronchodilator therapy, both long acting and short acting, is essential during the program. Patients may require administration of short acting bronchodilator at the beginning of the exercises or during the workout. For a successful outcome of endurance training it is important that patient gets trained on similar oxygen delivery device that they use at home and are on optimal management of COPD. A stable respiratory function will allow the patients to tolerate higher intensity workout for longer duration.
\nApart from improvement in endurance, COPD patients benefit from increase in their muscle strength [26, 83, 86, 87] . Increased muscle strength provides the patients with an ability to handle the ADLs better, improves their gait and reduce fall risk, thereby making them more independent [88]. A recent meta-analysis investigating different methods of PR in COPD showed greater improvement in HRQoL by adding strength training than endurance training alone [89]. Physiologically improving muscle strength in COPD patients can lead to increase in physical endurance, 6-minute walk distance and maximum oxygen consumption [90, 91]. Strength training is most beneficial if directed at muscles involved in functional living. This involves training muscles in upper and lower extremities as well as the trunk.
\nIt has been well proven that exercise training of the lower extremities leads to significant improvement in ambulatory stamina in COPD patients [42, 67, 92, 93, 94]. This is because lower extremities suffer most from disease-related muscular dystrophy in COPD patients. Additionally increasing lower extremity strength can reduce falls and maintain bone mineral density in COPD patients [45]. General recommendation to improve lower extremity strength is to provide resistance training with 2–4 sets of 10–15 repetitions of each exercise, for 2–3 days per week. Selection of weight for this type of resistance training workout is individualized based on patient’s capacity. Increment in the weight is done gradually once patient is able to accomplish all sets of exercise with a prescribed weight [45]. Lower extremity training can be achieved using walking, bicycling with incremental loads, stair climbing, swimming, weight machines or elastic bands. Choice is driven by available resources at the training site.
\nPatients suffering from COPD who have hyperinflation and flattened diaphragm have limitation in using their upper extremities to perform ADLs. Elevation of arms can result in increased ventilatory and metabolic demands in COPD patients with low respiratory reserves. This is thought to be because some of the upper extremity muscles also serve as accessory muscles of respiration [95, 96, 97]. Majority of the published literature on pulmonary rehabilitation suggests beneficial effect of upper extremity training in COPD patients. Some of the observed benefits of this training include improved upper extremity strength, which is task specific, decreased ventilatory demands and more independence in performing ADLs. Despite these observed benefits, optimal prescription of upper extremity training remains unclear.
\nPhysical therapists have to be mindful that in training the upper extremities, COPD patients may have elevated ventilatory work, asynchronous breathing and more dyspnea for the level of work. It is prudent to start with low resistance and frequent repetitions before gradually increasing the weight [81]. Upper extremity and trunk muscle strength training is achieved by using light weights (dumbbells, elastic bands), weight machines for stronger patients, rowing machines etc. Several of these instruments can also provide aerobic exercise training thereby improving both strength and endurance in the upper extremities.
\nPhysical therapists may provide training of upper and lower extremities on alternate days to improve patient tolerance. Progressive improvement in muscle strength is documented using standardized lifting tests, incremental resistive load tolerated by the patient and increased capacity in performing ADLs efficiently [86].
\nMany COPD patients suffer from modification in the structure of their chest wall due to hyperinflation, hypertrophy of the accessory respiratory muscles and physical inactivity. This further leads to changes in the posture and reduced mobility. To prevent this from happening, COPD patients undergo flexibility training as a part of the pulmonary rehabilitation program.
\nFlexibility exercises lead to improved mobility by increasing joint range of motion, reducing joint stiffness, better posture and increment in vital capacity [45]. Gentle stretching exercises with full body movements, coordinated with breathing techniques are appropriate for COPD patients [65, 98, 99].
\nThis kind of workout teaches the patient the influence of body movements on respiration. Since these exercises are done at a slower pace without any resistive loads, they can be used during warm up or cool down periods of the program. Limited research has been done on adequate duration and intensity of stretching exercises. General recommendation are to perform stretching of major muscle groups in the upper and lower extremities 2–3 days per week at the minimum [100]. Benefits of this training can be measured by documenting reduction in subjective perception of stiffness, reduced incidence of back pain and joint injuries.
\nTo provide a holistic care, every pulmonary rehabilitation program should incorporate patient education. It has been well proven that COPD patients who are well aware about the nature of their disease, its management and long-term implications are able to cope with both the disease and treatment better [101]. Education about the disease empowers the COPD patients to better recognize their symptoms, make lifestyle changes and get involved in the management of the disease. This leads to increased motivation to participate in pulmonary rehabilitation and adhere to the exercise regimen.
\nAt the beginning of the rehabilitation program, individual educational needs of each patient are identified. This is continuously reassessed while the patients are undergoing the rehabilitation program. Instead of a didactic teaching, a patient centered and self-management teaching approach focusing on lifelong behavioral changes are adopted these days [45]. Specifically for COPD patients, a collaborative self-management plan which helps them in an identification of symptoms of onset of an exacerbation, make treatment modification and to communicate early with a healthcare provider, is highly beneficial in the long run [102]. Patient education runs alongside the exercise training. It is meant to supplement the knowledge gaps and instill confidence in the principles of ongoing training. Various topics regarding disease and its management are covered with utilization of the expertise of various specialists.
\nExacerbation of COPD is an additional burden on patient’s already weakened functional capacity. It leads to hospitalization, further inactivity, deterioration of lung capacity and mortality. It may also disrupt any advances the patient may have made in improving their exercise capacity and muscle strength [45, 46]. There is an emerging data suggesting that there is benefit in instituting and/or continuing with pulmonary rehabilitation during hospital admission or within a month of hospital discharge. An early initiation of pulmonary rehabilitation reduces risk of re-hospitalization and improves overall symptoms without any adverse effects [103].
\nA pulmonary rehabilitation program incorporating occupational therapy is important in COPD patients [104, 105]. Occupational therapy assists COPD patients with development of specific strategies to perform ADLs with least expenditure of energy [106]. With conservation of energy expenditure, there is an improvement in subjective perception of breathlessness, increased efficiency in performing daily basic activities, elevated sense of control and better social engagement [104, 105, 106, 107]. Occupational therapy skills even though simple in principle, require a learning process, which is achieved through a multidisciplinary rehabilitation program. There is an ever-increasing evidence that improvement in occupation performance of COPD patients lead to a holistic improvement in their health [108]. Occupational therapist can also instruct COPD patient to use wheeled walking aids, which can result in increased functional autonomy, ventilatory capacity and waling efficiency [109, 110, 111, 112]. Since this therapy has a major impact on social networking of COPD patients, it serves well to involve patient’s family and friends [113].
\nBody composition in COPD patients may change as the disease severity progresses. While obesity predominates in the milder stages of the disease, patients with advanced disease and emphysema tend to be underweight and have generalized muscle wasting [114, 115]. Factors other than the lung disease itself, which can lead to this shift, includes inactivity, systemic inflammation, osteoporosis and glucocorticoids use. Studies have shown an increase in mortality in COPD patients who are underweight, independent of their disease severity [116, 117]. These patients with decreased fat free mass have higher limitation to exercise tolerance and thereby reported a decreased HRQoL status in comparison to COPD patients with normal weight [118, 119, 120, 121]. Various studies have shown a survival benefit with weight gain as low as 2 kg or by increase in one body mass index unit [116, 117]. This is why nutritional education are particularly essential in rehabilitation of COPD patients.
\nEvery pulmonary rehabilitation program should include nutritional screening with measurement of BMI at the least. A more comprehensive program may also include fat free mass estimate using skinfold anthropometry or bioimpedance analysis. Estimation of osteoporosis can be done using dual energy X-ray absorptiometry (DEXA) scanning. Improvement of nutritional status requires a multi-pronged approach with utilization of both physiologic and pharmacological interventions. Endurance and strength training as described previously in this chapter can improve muscle mass as well as bone strength. Nutritional interventions include adding nutritional supplementation to patient’s diet with emphasis on adequate protein intake to maintain or restore lean body mass. Patients who are unable to eat large meals due to dyspnea can switch to frequent small meals. It has been shown that a 6-month intervention involving dietary counseling, nutritional supplementation and positive reinforcement led to a significant weight gain in advanced COPD patients [60].
\nMany COPD patients who are referred to pulmonary rehabilitation suffer from depression and anxiety [45, 122]. Recent studies have estimated prevalence of depressed mood in about 45% and anxiety in 32% of patients with moderate to advanced COPD [123, 124, 125]. Dyspnea on exertion leads to fear and anxiety anytime a COPD patient has to exercise. This severely limits their social interaction and eventually leads to depression. COPD patients can suffer from hopelessness, sense of isolation and lack of motivation. It is essential to assess the presence of depressed mood during initial evaluation in a pulmonary rehabilitation program. Family and caregiver involvement is advisable to assess the social support system for the patient.
\nIdentifying the mood disorders and deficit in the social support is an integral part of the program [114]. Patients in need can be provided with psychological and social support, which works to elevate mood, positive thinking and adaptive behavior towards disease and its management. This also improves the compliance with the pulmonary rehabilitation program. Psychological support can be provided by the physical therapist but often require a psychologist or a psychiatrist involvement.
\nVarious models of PR have been adopted worldwide. An outpatient or hospital based-outpatient setting is the most widely used model to deliver PR to COPD patient in the developed countries [126]. Current body of evidence regarding effectiveness of PR in COPD patients is based on this model. In recent years an alternative model where the site of delivery of PR is at home has been studied. Home based PR setting provides the benefit of exercise training in a familiar setting to a larger patient population. Specifically for patients with severe COPD dependent on long term oxygen therapy, this model of PR has been shown to be both safe and effective [127, 128]. While home based PR model offers convenience, it lacks the group dynamics which an outpatient model can offer. Group therapy leads to socialization, mood elevation and positive reinforcement. Additionally a home based program does not have a multidisciplinary and comprehensive structure of a hospital based outpatient setting. At the present time, choice of location of PR is dependent on patient preference, disease severity and regional availability of resources.
\nSeveral COPD patients with advanced lung disease who are bed bound or wheelchair bound are unable to participate in a conventional pulmonary rehabilitation program. To help these patients, a new modality of transcutaneous neuromuscular electrical stimulation (NMES) has been devised recently [129, 130, 131]. This technology involves application of low amplitude electric current via electrodes transcutaneously to the targeted muscle groups by depolarizing motor neurons. Low intensity electric current (10–100 mA) is delivered at stimulation frequencies between 8 and 120 Hz for duration of 250–400 ms. Although no large RCTs are available, a recent meta-analysis did report improvement in quadriceps strength and exercise capacity with NMES. Unfortunately, no significant improvement in HRQoL in moderate to severe COPD was seen [132]. Apart from debilitated COPD patients, this technology has been recommended for use during COPD exacerbation, as it has low impact on ventilation, heart rate and dyspnea [133, 134].
\nA pulmonary rehabilitation programs for COPD patients usually includes respiratory muscle training. The goal of this training is to improve the abnormal breathing pattern, which may result due to increased work of breathing, chest wall changes and poor breathing habits in COPD patients [135, 136, 137, 138]. The most commonly applied approach is through the endurance and strength training. [26]. Exercise training can lead to increase in minute ventilation, which leads to an increase in work of breathing. Constant controlled aerobic exercises of upper and lower extremities can lead to a recurrent stimulation to respiratory muscles. This helps the COPD patients to modify their breathing patterns on a day-to-day basis as well as be better prepared for an exacerbation.
\nApart from exercise training, specific breathing exercises such as diaphragmatic breathing, paced breathing with exercises and pursed lip breathing has been proven to be beneficial in COPD patients. Diaphragm, which is the main inspiratory muscle, is flattened and ineffective in patients with hyperinflated lungs. This puts these patients at a mechanical disadvantage to adequately maintain and increase their minute ventilation. COPD patients who undergo the training to improve the coordination of their diaphragmatic muscle tend to fare better overall [139].
\nMany patients with emphysema self-discover the method of purse lip breathing for faster recovery from shortness of breath post exercise. Other patients can be instructed regarding this method. It helps patients to increase alveolar ventilation, tidal volume and CO2 removal. It also leads to slow expiratory flow and decreased respiratory rate [140]. Using the same principle, respiratory muscles can be trained by using resistive breathing devices. This can be particularly useful in patients who continue to have dyspnea despite optimal medical management.
\nAdditionally COPD patients specifically with chronic bronchitis occasionally have ineffectual cough leading to difficulty in respiratory secretion clearance. Instructions on special coughing techniques (huffing, autogenic drainage) combined with oscillating expiratory breathing devices (Acapella, In-exsufflator) can prove effective [141]. Patients can be instructed to perform daily chest physiotherapy to assist in respiratory secretion clearance through postural drainage techniques [142]. A meta-analysis of 32 studies focusing on respiratory muscle training showed that it leads to improvement in respiratory muscle strength, exercise capacity and perception of exertional dyspnea [143].
\nThe beneficial effects of a comprehensive pulmonary rehabilitation program are not sustained beyond 12 months [32, 42, 144, 145]. On the other hand, repeating a pulmonary rehabilitation programs has not been found to be an effective treatment option [146]. Considering this, it is challenging to maintain the changes made in physical activity and lifestyle due to a pulmonary rehabilitation. Although there is a lack of data on maintenance programs, some centers do provide these in the hope to achieve prolonged benefits gathered in a successful rehabilitation program. There are no set guidelines to establish an optimal strategy for providing maintenance pulmonary rehabilitation. Additionally other factors such as lack of transportation to the PR center, disruption of daily life routine, absence of family support, perception regarding gains from the PR program, have impact on patient’s participation in the post PR programs. A recent multicenter RCT studying the long term (3 year) maintenance program after PR in severe COPD patients, showed a sustained beneficial effect on BODE index and 6MWD at 24 months. Although, the effect vanished beyond 2 years as at end of study only 66% of COPD patients were still adherent with the maintenance program [147].
\nVarious methods adopted to provide therapy beyond a comprehensive program include weekly telephone contacts, home exercise training with or without weekly-supervised outpatient sessions and recurrent PR program [146, 148, 149, 150, 151]. A recent meta-analysis analyzing post-PR exercise program in COPD patients suggested that such a program even though effective in maintaining a good exercise capacity with the 6 months of PR, loses its benefit beyond 1 year and has no impact on HRQoL [152]. The patient population and the interventions used were variable and results of this study need to be interpreted cautiously.
\nSince the structure of the most effective maintenance program remains elusive, it is important at this time to encourage the COPD patients to continue with healthy lifestyle changes. This can be achieved by a concerted effort of the PR staff, family members, and patients’ healthcare team. Those COPD patients who continue with the exercise routine and lifestyle changes they had learnt in the PR program tend to accumulate gains in physical endurance and psychological functioning [153].
\nPulmonary rehabilitation has a major role in the management of patients with chronic lung conditions especially COPD. The need for more convenient and efficient programs using new technology would be beneficial for patients. Tele-rehabilitation to deliver rehabilitation services over telemedicine using internet or phone can provides services to patients who live in remote areas without access to transportation. Tele-rehabilitation allows video conferencing between a central control unit and a patient at home. This will also deliver health services to patients with disability who cannot travel long distances for rehabilitation programs. Both mobile phones and video conferencing have used in few studies deliver rehabilitation services. The studies have demonstrated good compliance, decrease in exacerbations and hospitalizations, improved exercise capacity and quality of life [154, 155]. Benefits of telemonitoring in COPD patients have been described in a systemic review that showed decrease in hospitalizations and emergency room visits using telephone support for telerehabilitation [156].
\nA comprehensive multimodality pulmonary rehabilitation program is becoming an essential part of the management of COPD patients. It is not only cost effective but also scientifically proven to improve patients’ symptoms and functionality. With a gradual increase in daily activity, COPD patients are able to achieve higher HRQoL compared to pharmacotherapy alone. Despite these proven benefits, widespread utilization of PR remains poor. Multiple factors, including; physician unfamiliarity of benefits of PR, patient compliance with the exercise regimen and insurance coverage contribute to this gap. With the increasing prevalence of COPD worldwide, a safe and effective option like PR needs to be actively promoted and utilized.
\nApart from standardized exercise regimens and strength training, the emphasis of an effective PR program is on behavioral modification. This result in long lasting, positive changes on the disease course. In addition, empowering the COPD patients by educating them about disease, smoking cessation and nutrition is a crucial step in the right direction. Development of home based or telerehabilitation services may assist in reducing the disparity in access to PR for many more COPD patients.
\nAuthors declare no conflicts of interest.
\n chronic obstructive pulmonary disease acute exacerbation of chronic obstructive pulmonary disease pulmonary rehabilitation health-related quality of life randomized controlled trial neuromuscular electrical stimulation activities of daily living modified Medical Research Council 6 minute walk test functional independence measure assessment of motor and process skills functional capacity evaluation dual energy X-ray absorptiometry body mass index, airflow obstruction, dyspnea and exercise capacity
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